Th17 differentiation and their pro-inflammation function

Advances in Experimental Medicine and Biology

Volumn 841, Issue , 2014, Pages 99-151

  Song, Xinyang ^a   Gao, Hanchao ^a   Qian, Youcun ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

IL 17; IL 22; Inflammation; T cell differentiation; Th17 cells

Indexed keywords

INTERFERON REGULATORY FACTOR 4; INTERLEUKIN 17; INTERLEUKIN 17C; INTERLEUKIN 17F; INTERLEUKIN 1BETA; INTERLEUKIN 21; INTERLEUKIN 23; INTERLEUKIN 6; LIVER X RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; MICRORNA; PROTEIN GFI1; PROTEIN NFIL3; RETINOID RELATED ORPHAN RECEPTOR ALPHA; RETINOID RELATED ORPHAN RECEPTOR GAMMA; STAT3 PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR 7; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CYTOKINE; TARGET OF RAPAMYCIN KINASE;

ALLERGY; AUTOIMMUNE DISEASE; CELL DIFFERENTIATION; CELL INTERACTION; EPIGENETICS; GENE EXPRESSION REGULATION; GENETIC REGULATION; HELPER CELL; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; INFECTION RESISTANCE; LYMPHOCYTE FUNCTION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH17 CELL; TH2 CELL; ANIMAL; CYTOLOGY; IMMUNOLOGY; INFLAMMATION; NEOPLASM; PHYSIOLOGY;

ANIMALS; AUTOIMMUNE DISEASES; CELL DIFFERENTIATION; CYTOKINES; HUMANS; INFLAMMATION; NEOPLASMS; T-LYMPHOCYTES, REGULATORY; TH17 CELLS; TOR SERINE-THREONINE KINASES; TRANSCRIPTION FACTORS;

EID: 84922544266     PISSN: 00652598     EISSN: 22148019     Source Type: Book Series    
DOI: 10.1007/978-94-017-9487-9_5     Document Type: Chapter

References (337)

1. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8(9):942–949. doi:10.1038/ni1496
2. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278(3):1910–1914. doi:10.1074/jbc.M207577200
3. Al-Ramli W, Prefontaine D, Chouiali F, Martin JG, Olivenstein R, Lemiere C, Hamid Q (2009) T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 123(5):1185–1187. doi:10.1016/j.jaci.2009.02.024
4. Albanesi C, Cavani A, Girolomoni G (1999) IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. Journal of immunology 162(1):494–502
5. Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, De Benedetti F, Poli V, Ciliberto G (1998) Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 187(4):461–468
6. Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129(3):969–984. doi:10.1053/j.gastro.2005.06.071
7. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204(8):1849–1861. doi:10.1084/jem.20070663
8. Ansel KM, Lee DU, Rao A (2003) An epigenetic view of helper T cell differentiation. Nat Immunol 4(7):616–623. doi:10.1038/ni0703-616
9. Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K, Takeda K (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808–812. doi:10.1038/nature07240
10. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK (2008) IL-22 mediates mucosal host defense against gram-negative bacterial pneumonia. Nat Med 14(3):275–281. doi:10.1038/nm1710
11. Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, Sturton G, Wong SH, McKenzie AN (2007) Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 120(6):1324–1331. doi:10.1016/j.jaci.2007.07.051
12. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Consortium NIG, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Belgian-French IBDC, Wellcome Trust Case Control C, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40(8):955–962. doi:10.1038/ng.175
13. Batten M, Li J, Yi S, Kljavin NM, Danilenko DM, Lucas S, Lee J, de Sauvage FJ, Ghilardi N (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 7(9):929–936. doi:10.1038/ni1375
14. Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11(9):372–377
15. Bending D, De la Pena H, Veldhoen M, Phillips JM, Uyttenhove C, Stockinger B, Cooke A (2009) Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 119(3):565–572. doi:10.1172/JCI37865
16. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238. doi:10.1038/nature04753
17. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK (2004) Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 200(1):79–87. doi:10.1084/jem.20031819
18. Beyeen AD, Adzemovic MZ, Ockinger J, Stridh P, Becanovic K, Laaksonen H, Lassmann H, Harris RA, Hillert J, Alfredsson L, Celius EG, Harbo HF, Kockum I, Jagodic M, Olsson T (2010) IL-22RA2 associates with multiple sclerosis and macrophage effector mechanisms in experimental neuroinflammation. Journal of immunology 185(11):6883–6890. doi:10.4049/jimmunol.1001392
19. Brand DD, Latham KA, Rosloniec EF (2007) Collagen-induced arthritis. Nat Protoc 2(5):1269–1275. doi:10.1038/nprot.2007.173
20. Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J (2006) IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 290(4):G827–838. doi:10.1152/ajpgi.00513.2005
21. Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C, Yu P, Arpaia E, Mak TW, Kamradt T, Lohoff M (2007) The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8(9):958–966. doi:10.1038/ni1500
22. Bulek K, Liu C, Swaidani S, Wang L, Page RC, Gulen MF, Herjan T, Abbadi A, Qian W, Sun D, Lauer M, Hascall V, Misra S, Chance MR, Aronica M, Hamilton T, Li X (2011) The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol 12(9):844–852. doi:10.1038/ni.2080
23. Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80(2):273–290. doi:10.1086/511051
24. Carmi Y, Rinott G, Dotan S, Elkabets M, Rider P, Voronov E, Apte RN (2011) Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis. J immunol 186(6):3462–3471. doi:10.4049/jimmunol.1002901
25. Chae WJ, Bothwell AL (2011) IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochem Biophys Res Commun 414(1):31–36. doi:10.1016/j.bbrc.2011.09.016
26. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL (2010) Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 107(12):5540–5544. doi:10.1073/pnas.0912675107
27. Chang SH, Park H, Dong C (2006) Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem 281(47):35603–35607. doi:10.1074/jbc.C600256200
28. Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C (2011) Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 35(4):611–621. doi:10.1016/j.immuni.2011.09.010
29. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB (2008) IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity 29(6):899–911. doi:10.1016/j.immuni.2008.10.011
30. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4 + CD25- naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875–1886. doi:10.1084/jem.20030152
31. Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O’Shea JJ (2006) Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA 103(21):8137–8142. doi:10.1073/pnas.0600666103
32. Cheng F, Guo Z, Xu H, Yan D, Li Q (2009) Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 68(4):604–606. doi:10.1136/ard.2008.097089
33. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D (1995) Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science 267(5203):1494–1498
34. Chiricozzi A, Guttman-Yassky E, Suarez-Farinas M, Nograles KE, Tian S, Cardinale I, Chimenti S, Krueger JG (2011) Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131(3):677–687. doi:10.1038/jid.2010.340
35. Chitnis T, Najafian N, Benou C, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ (2001) Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 108(5):739–747. doi:10.1172/JCI12563
36. Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, Dong C (2009) Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30(4):576–587. doi:10.1016/j.immuni.2009.02.007
37. Ciccacci C, Biancone L, Di Fusco D, Ranieri M, Condino G, Giardina E, Onali S, Lepre T, Pallone F, Novelli G, Borgiani P (2012) TRAF3IP2 gene is associated with cutaneous extraintestinal manifestations in Inflammatory Bowel Disease. J Crohns Colitis. doi:10.1016/j.crohns.2012.02.020
38. Claudio E, Sonder SU, Saret S, Carvalho G, Ramalingam TR, Wynn TA, Chariot A, Garcia-Perganeda A, Leonardi A, Paun A, Chen A, Ren NY, Wang H, Siebenlist U (2009) The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation. J immunol 182(3):1617–1630
39. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O’Connor E, Godwin J, Wilson CB, Brockdorff N, Fisher AG, Smale ST, Merkenschlager M (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201(9):1367–1373. doi:10.1084/jem.20050572
40. Conforti-Andreoni C, Spreafico R, Qian HL, Riteau N, Ryffel B, Ricciardi-Castagnoli P, Mortellaro A (2011) Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18. J immunol 187(11):5842–5850. doi:10.4049/jimmunol.1101408
41. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, Powrie F (2007) A functionally specialized population of mucosal CD103 + DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204(8):1757–1764. doi:10.1084/jem.20070590
42. Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI (2008) Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J immunol 180(11):7097–7101
43. Crispin JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, Kyttaris VC, Juang YT, Tsokos GC (2008) Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J immunol 181(12):8761–8766
44. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744–748. doi:10.1038/nature01355
45. Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10(7):479–489. doi:10.1038/nri2800
46. Cui G, Qin X, Wu L, Zhang Y, Sheng X, Yu Q, Sheng H, Xi B, Zhang JZ, Zang YQ (2011) Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest 121(2):658–670. doi:10.1172/JCI42974
47. da Rocha LF, Jr., Duarte AL, Dantas AT, Mariz HA, Pitta Ida R, Galdino SL, Pitta MG (2012) Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity. J Rheumatol 39(7):1320–1325. doi:10.3899/jrheum.111027
48. Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G (2009) Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 206(11):2407–2416. doi:10.1084/jem.20082286
49. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, Feinberg J, von Bernuth H, Samarina A, Janniere L, Fieschi C, Stephan JL, Boileau C, Lyonnet S, Jondeau G, Cormier-Daire V, Le Merrer M, Hoarau C, Lebranchu Y, Lortholary O, Chandesris MO, Tron F, Gambineri E, Bianchi L, Rodriguez-Gallego C, Zitnik SE, Vasconcelos J, Guedes M, Vitor AB, Marodi L, Chapel H, Reid B, Roifman C, Nadal D, Reichenbach J, Caragol I, Garty BZ, Dogu F, Camcioglu Y, Gulle S, Sanal O, Fischer A, Abel L, Stockinger B, Picard C, Casanova JL (2008) Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med 205(7):1543–1550. doi:10.1084/jem.20080321
50. De Luca A, Zelante T, D’Angelo C, Zagarella S, Fallarino F, Spreca A, Iannitti RG, Bonifazi P, Renauld JC, Bistoni F, Puccetti P, Romani L (2010) IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol 3(4):361–373. doi:10.1038/mi.2010.22
51. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao B, Worley PF, Powell JD (2011) The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 12(4):295–303. doi:10.1038/ni.2005
52. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. doi:10.1146/annurev.immunol.021908.132612
53. Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM (2007) Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 8(2):145–153. doi:10.1038/ni1424
54. Doe C, Bafadhel M, Siddiqui S, Desai D, Mistry V, Rugman P, McCormick M, Woods J, May R, Sleeman MA, Anderson IK, Brightling CE (2010) Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 138(5):1140–1147. doi:10.1378/chest.09-3058
55. Dong G, Ye R, Shi W, Liu S, Wang T, Yang X, Yang N, Yu X (2003) IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Med J 116(4):543–548
56. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10(12):1252–1259. doi:10.1038/ni.1798
57. Du J, Huang C, Zhou B, Ziegler SF (2008) Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3. J Immunol 180(7):4785–4792
58. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463. doi:10.1126/science.1135245
59. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O’Shea JJ (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32(5):605–615. doi:10.1016/j.immuni.2010.05.003
60. Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, Belouchi M, Fournier H, Reinhard C, Ding J, Li Y, Tejasvi T, Gudjonsson J, Stoll SW, Voorhees JJ, Lambert S, Weidinger S, Eberlein B, Kunz M, Rahman P, Gladman DD, Gieger C, Wichmann HE, Karlsen TH, Mayr G, Albrecht M, Kabelitz D, Mrowietz U, Abecasis GR, Elder JT, Schreiber S, Weichenthal M, Franke A (2010) Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 42(11):991–995. doi:10.1038/ng.689
61. Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A, Shapiro AM (2009) Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58(6):1302–1311. doi:10.2337/db08-1113
62. Endo Y, Iwamura C, Kuwahara M, Suzuki A, Sugaya K, Tumes DJ, Tokoyoda K, Hosokawa H, Yamashita M, Nakayama T (2011) Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3. Immunity 35(5):733–745. doi:10.1016/j.immuni.2011.08.017
63. Eshima K, Chiba S, Suzuki H, Kokubo K, Kobayashi H, Iizuka M, Iwabuchi K, Shinohara N (2012) Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4(+) Th cells cytotoxic by activating both perforin- and FasL-pathways. Immunol Lett 144(1–2):7–15. doi:10.1016/j.imlet.2012.02.013
64. Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, McIlgorm A, Jolin HE, McKenzie AN (2006) Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med 203(4):1105–1116. doi:10.1084/jem.20051615
65. Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, Ohsugi Y, Nishikawa T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis Rheum 58(12):3710–3719. doi:10.1002/art.24126
66. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52(1):65–70
67. Furlan R, Martino G, Galbiati F, Poliani PL, Smiroldo S, Bergami A, Desina G, Comi G, Flavell R, Su MS, Adorini L (1999) Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J Immunol 163(5):2403–2409
68. Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9(8):556–567. doi:10.1038/nri2586
69. Garg AV, Ahmed M, Vallejo AN, Ma A, Gaffen SL (2013) The deubiquitinase a20 mediates feedback inhibition of interleukin-17 receptor signaling. Science Signal 6(278):ra44. doi:10.1126/scisignal.2003699
70. Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445(7129):771–775. doi:10.1038/nature05543
71. Geboes L, Dumoutier L, Kelchtermans H, Schurgers E, Mitera T, Renauld JC, Matthys P (2009) Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum 60(2):390–395. doi:10.1002/art.24220
72. Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Mazurov V, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Mpofu S (2013) Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 72(6):863–869. doi:10.1136/annrheumdis-2012-201601
73. Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, Sloan-Lancaster J (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62(4):929–939. doi:10.1002/art.27334
74. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O’Shea JJ (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467(7318):967–971. doi:10.1038/nature09447
75. Gopal M, da Cunha AP, Weiner HL (2013) 97: Silencing MicroRNA-21 ameliorates Th17 mediated autoimmune inflammation. Cytokine 63(3):266
76. Gordon SM, Carty SA, Kim JS, Zou T, Smith-Garvin J, Alonzo ES, Haimm E, Sant’Angelo DB, Koretzky GA, Reiner SL, Jordan MS (2011) Requirements for eomesodermin and promyelocytic leukemia zinc finger in the development of innate-like CD8 + T cells. J Immunol 186(8):4573–4578. doi:10.4049/jimmunol.1100037
77. Gorelik L, Fields PE, Flavell RA (2000) Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. J Immunol 165(9):4773–4777
78. Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A (2002) IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of nervous system autoimmune demyelination. J Immunol 169(12):7104–7110
79. Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, Huang M, Schneider M, Miller SD, Ting JP (2010) NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol 185(2):974–981. doi:10.4049/jimmunol.0904145
80. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491(7423):254–258 nature11465 [pii]10.10348/nature11465
81. Gulen MF, Bulek K, Xiao H, Yu M, Gao J, Sun L, Beurel E, Kaidanovich-Beilin O, Fox PL, DiCorleto PE, Wang JA, Qin J, Wald DN, Woodgett JR, Jope RS, Carman J, Dongre A, Li X (2012) Inactivation of the enzyme GSK3alpha by the kinase IKKi promotes AKT-mTOR signaling pathway that mediates interleukin-1-induced Th17 cell maintenance. Immunity 37(5):800–812. doi:10.1016/j.immuni.2012.08.019
82. Gulen MF, Kang Z, Bulek K, Youzhong W, Kim TW, Chen Y, Altuntas CZ, Sass Bak-Jensen K, McGeachy MJ, Do JS, Xiao H, Delgoffe GM, Min B, Powell JD, Tuohy VK, Cua DJ, Li X (2010) The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity 32(1):54–66. doi:10.1016/j.immuni.2009.12.003
83. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466(7308):835–840. doi:10.1038/nature09267
84. Gutcher I, Donkor MK, Ma Q, Rudensky AY, Flavell RA, Li MO (2011) Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity 34(3):396–408. doi:10.1016/j.immuni.2011.03.005
85. Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Hacker G, Mann M, Karin M (2006) Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439(7073):204–207. doi:10.1038/nature04369
86. Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, Purdy D, Fitch E, Iordanov M, Blauvelt A (2009) Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129(9):2175–2183. doi:10.1038/jid.2009.65
87. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6(11):1123–1132. doi:10.1038/ni1254
88. Harris TJ, Grosso JF, Yen HR, Xin H, Kortylewski M, Albesiano E, Hipkiss EL, Getnet D, Goldberg MV, Maris CH, Housseau F, Yu H, Pardoll DM, Drake CG (2007) Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 179(7):4313–4317
89. Hartupee J, Liu C, Novotny M, Sun D, Li X, Hamilton TA (2009) IL-17 signaling for mRNA stabilization does not require TNF receptor-associated factor 6. J Immunol 182(3):1660–1666
90. Hata H, Sakaguchi N, Yoshitomi H, Iwakura Y, Sekikawa K, Azuma Y, Kanai C, Moriizumi E, Nomura T, Nakamura T, Sakaguchi S (2004) Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 114(4):582–588. doi:10.1172/JCI21795
91. He D, Li H, Yusuf N, Elmets CA, Athar M, Katiyar SK, Xu H (2012) IL-17 mediated inflammation promotes tumor growth and progression in the skin. PLoS ONE 7(2):e32126. doi:10.1371/journal.pone.0032126
92. He JQ, Zarnegar B, Oganesyan G, Saha SK, Yamazaki S, Doyle SE, Dempsey PW, Cheng G (2006) Rescue of TRAF3-null mice by p100 NF-kappa B deficiency. J Exp Med 203(11):2413–2418 (jem.20061166 [pii]/jem.20061166)
93. He YW, Deftos ML, Ojala EW, Bevan MJ (1998) RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells. Immunity 9(6):797–806
94. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(Pt 1):1–20. doi:10.1042/BJ20030407
95. Hemdan NY, Birkenmeier G, Wichmann G (2012) Key molecules in the differentiation and commitment program of T helper 17 (Th17) cells up-to-date. Immunol Lett 148(2):97–109. doi:10.1016/j.imlet.2012.09.007
96. Herjan T, Yao P, Qian W, Li X, Liu C, Bulek K, Sun D, Yang WP, Zhu J, He A, Carman JA, Erzurum SC, Lipshitz HD, Fox PL, Hamilton TA, Li X (2013) HuR Is Required for IL-17-Induced Act1-Mediated CXCL1 and CXCL5 mRNA Stabilization. J Immunol. doi:10.4049/jimmunol.1203315
97. Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M et al (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18(11):1797–1801. doi:10.1002/eji.1830181122
98. Ho AW, Shen F, Conti HR, Patel N, Childs EE, Peterson AC, Hernandez-Santos N, Kolls JK, Kane LP, Ouyang W, Gaffen SL (2010) IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail. J Immunol 185(2):1063–1070 jimmunol.0903739 [pii]/jimmunol.0903739
99. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357(16):1608–1619. doi:10.1056/NEJMoa073687
100. Hu Y, Ota N, Peng I, Refino CJ, Danilenko DM, Caplazi P, Ouyang W (2010) IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 184(8):4307–4316. doi:10.4049/jimmunol.0903614
101. Huang F, Kao CY, Wachi S, Thai P, Ryu J, Wu R (2007) Requirement for both JAK-mediated PI3 K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol 179(10):6504–6513
102. Huber M, Brustle A, Reinhard K, Guralnik A, Walter G, Mahiny A, von Low E, Lohoff M (2008) IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci USA 105(52):20846–20851. doi:10.1073/pnas.0809077106
103. Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Psoriasis Study G, Durez P, Tak PP, Gomez-Reino JJ, Rheumatoid Arthritis Study G, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Uveitis Study G, Rose K, Haider A, Di Padova F (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Science translational medicine 2 (52):52ra72. doi:10.1126/scitranslmed.3001107
104. Huffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, Juneblad K, Apel M, McManus R, Ho P, Bruce IN, Ryan AW, Behrens F, Lascorz J, Bohm B, Traupe H, Lohmann J, Gieger C, Wichmann HE, Herold C, Steffens M, Klareskog L, Wienker TF, Fitzgerald O, Alenius GM, McHugh NJ, Novelli G, Burkhardt H, Barton A, Reis A (2010) Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 42(11):996–999. doi:10.101038/ng.688
105. Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, Menon S, Seymour B, Jackson C, Kung TT, Brieland JK, Zurawski SM, Chapman RW, Zurawski G, Coffman RL (2002) New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 169(1):443–453
106. Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY (2012) Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 33(4):931–936. doi:10.1093/carcin/bgs106
107. Ichiyama K, Hashimoto M, Sekiya T, Nakagawa R, Wakabayashi Y, Sugiyama Y, Komai K, Saba I, Moroy T, Yoshimura A (2009) Gfi1 negatively regulates T(h)17 differentiation by inhibiting RORgammat activity. Int Immunol 21(7):881–889. doi:10.1093/intimm/dxp054
108. Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, Yoshimura A (2011) Transcription factor Smad-independent T helper 17 cell induction by transforming-growth factor-beta is mediated by suppression of eomesodermin. Immunity 34(5):741–754. doi:10.1016/j.immuni.2011.02.021
109. Inoue M, Williams KL, Gunn MD, Shinohara ML (2012) NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 109(26):10480–10485. doi:10.1073/pnas.1201836109
110. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30(1):108–119. doi:10.1016/j.immuni.2008.11.009
111. Ito A, Bebo BF Jr, Matejuk A, Zamora A, Silverman M, Fyfe-Johnson A, Offner H (2001) Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J Immunol 167(1):542–552
112. Ito R, Kita M, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Iwakura Y, Okanoue T, Yoshikawa T, Kataoka K, Mazda O (2008) Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. Biochem Biophys Res Commun 377(1):12–16. doi:10.1016/j.bbrc.2008.09.019
113. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485–498. doi:10.1016/j.cell.2009.09.033
114. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17 + T helper cells. Cell 126(6):1121–1133. doi:10.1016/j.cell.2006.07.035
115. Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34(2):149–162. doi:10.1016/j.immuni.2011.02.012
116. Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, Chen VS, Gris D, Matsushima GK, Ting JP (2010) The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci 30(47):15811–15820. doi:10.1523/JNEUROSCI.4088-10.2010
117. Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, Gao Y, Yao A, Wang X, Yu L, Sun B (2013) IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer 13:59. doi:10.1186/1471-2407-13-59
118. Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K (2009) Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 160(2):319–324. doi:10.1111/j.1365-2133.2008.08902.x
119. Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, Chen CS, Fu W, Gudjonsson JE, McCormick TS, Ward NL (2013) Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol 190(5):2252–2262. doi:10.4049/jimmunol.1201505
120. Joosten LA, Helsen MM, van de Loo FA, van den Berg WB (2008) Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFalpha, anti-IL-1alpha/beta and IL-1Ra. Arthritis Rheum 58(2 Suppl):S110–122. doi:10.1002/art.23363
121. Kang Z, Swaidani S, Yin W, Wang C, Barlow JL, Gulen MF, Bulek K, Do JS, Aronica M, McKenzie AN, Min B, Li X (2012) Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(−)c-Kit(+) innate cell population. Immunity 36(5):821–833. doi:10.1016/j.immuni.2012.03.021
122. Kawaguchi M, Kokubu F, Matsukura S, Ieki K, Odaka M, Watanabe S, Suzuki S, Adachi M, Huang SK (2003) Induction of C-X-C chemokines, growth-related oncogene alpha expression, and epithelial cell-derived neutrophil-activating protein-78 by ML-1 (interleukin-17F) involves activation of Raf1-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 pathway. J Pharmacology and experimental therapeutics 307(3):1213–1220. doi:10.1124/jpet.103.056341
123. Kim MR, Manoukian R, Yeh R, Silbiger SM, Danilenko DM, Scully S, Sun J, DeRose ML, Stolina M, Chang D, Van GY, Clarkin K, Nguyen HQ, Yu YB, Jing S, Senaldi G, Elliott G, Medlock ES (2002) Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Blood 100(7):2330–2340. doi:10.1182/blood-2002-01-0012
124. Kirigin FF, Lindstedt K, Sellars M, Ciofani M, Low SL, Jones L, Bell F, Pauli F, Bonneau R, Myers RM, Littman DR, Chong MM (2012) Dynamic microRNA gene transcription and processing during T cell development. J Immunol 188(7):3257–3267. doi:10.4049/jimmunol.1103175
125. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA (2013) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496(7446):518–522. doi:10.1038/nature11868
126. Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM, Blumenschein WM, McClanahan T, Brombacher F, Hurst SD, Kastelein RA, Cua DJ (2007) IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 204(1):161–170. doi:10.1084/jem.20061738
127. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, Sudo K, Iwakura Y (2006) IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177(1):566–573
128. Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, Oukka M, Kuchroo VK (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152):484–487. doi:10.1038/nature05970
129. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517. doi:10.1146/annurev.immunol.021908.132710
130. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103(9):1345–1352. doi:10.1172/JCI5703
131. Krajewski S, Zapata JM, Krajewska M, VanArsdale T, Shabaik A, Gascoyne RD, Reed JC (1997) Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family. J Immunol 159(12):5841–5852
132. Krakowski M, Owens T (1996) Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur J Immunol 26(7):1641–1646. doi:10.1002/eji.1830260735
133. Krawczyk CM, Shen H, Pearce EJ (2007) Functional plasticity in memory T helper cell responses. J Immunol 178(7):4080–4088
134. Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B (2007) IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 179(12):8098–8104
135. Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149. doi:10.1182/blood-2009-03-208249
136. Kryczek I, Wei S, Szeliga W, Vatan L, Zou W (2009) Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114(2):357–359. doi:10.1182/blood-2008-09-177360
137. Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D (2012) IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med 18(4):547–554. doi:10.1038/nm.2684
138. Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL, Aujla SJ, Reardon B, Moore M, Shea P, Schreckhise R, Bukowski TR, Presnell S, Guerra-Lewis P, Parrish-Novak J, Ellsworth JL, Jaspers S, Lewis KE, Appleby M, Kolls JK, Rixon M, West JW, Gao Z, Levin SD (2007) Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol 179(8):5462–5473
139. Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA, Dienger K, Budelsky AL, Wills-Karp M (2010) Complement-mediated regulation of the IL-17A axis is a genetic determinant of the severity of experimental allergic asthma. Nat Immunol 11(10):928–935. doi:10.1038/ni.1926
140. Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH (2011) Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity. J Immunol 186(10):5738–5748. doi:10.4049/jimmunol.1003597
141. Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006) IL-23 promotes tumour incidence and growth. Nature 442(7101):461–465. doi:10.1038/nature04808
142. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201(2):233–240. doi:10.1084/jem.20041257
143. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. doi:10.1016/j.cell.2012.03.017
144. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O’Shea JJ (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26(3):371–381. doi:10.1016/j.immuni.2007.02.009
145. Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH (2011) T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat. Nat Immunol 12(1):96–104. doi:10.1038/ni.1969
146. Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA, Boothby M (2010) Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32(6):743–753. doi:10.1016/j.immuni.2010.06.002
147. Lee YK, Turner H, Maynard CL, Oliver JR, Chen D, Elson CO, Weaver CT (2009) Late developmental plasticity in the T helper 17 lineage. Immunity 30(1):92–107. doi:10.1016/j.immuni.2008.11.005
148. Leonard JP, Waldburger KE, Goldman SJ (1995) Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J Exp Med 181(1):381–386
149. Lexberg MH, Taubner A, Forster A, Albrecht I, Richter A, Kamradt T, Radbruch A, Chang HD (2008) Th memory for interleukin-17 expression is stable in vivo. Eur J Immunol 38(10):2654–2664. doi:10.1002/eji.200838541
150. Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, Dowd P, Gurney AL, Wood WI (2000) Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci USA 97(2):773–778
151. Li MO, Flavell RA (2008) TGF-beta: a master of all T cell trades. Cell 134(3):392–404. doi:10.1016/j.cell.2008.07.025
152. Li MO, Sanjabi S, Flavell RA (2006) Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25(3):455–471. doi:10.1016/j.immuni.2006.07.011
153. Li MO, Wan YY, Flavell RA (2007) T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26(5):579–591. doi:10.1016/j.immuni.2007.03.014
154. Li Q, Han Y, Fei G, Guo Z, Ren T, Liu Z (2012) IL-17 promoted metastasis of non-small-cell lung cancer cells. Immunol Lett 148(2):144–150. doi:10.1016/j.imlet.2012.10.011
155. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203(10):2271–2279. doi:10.1084/jem.20061308
156. Lin Y, Ritchea S, Logar A, Slight S, Messmer M, Rangel-Moreno J, Guglani L, Alcorn JF, Strawbridge H, Park SM, Onishi R, Nyugen N, Walter MJ, Pociask D, Randall TD, Gaffen SL, Iwakura Y, Kolls JK, Khader SA (2009) Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 31(5):799–810. doi:10.1016/j.immuni.2009.08.025
157. Liu C, Qian W, Qian Y, Giltiay NV, Lu Y, Swaidani S, Misra S, Deng L, Chen ZJ, Li X (2009) Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Science signaling 2(92):ra63. doi:10.1126/scisignal.2000382
158. Liu C, Swaidani S, Qian W, Kang Z, Sun P, Han Y, Wang C, Gulen MF, Yin W, Zhang C, Fox PL, Aronica M, Hamilton TA, Misra S, Deng J, Li X (2011) A CC’ loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Science signaling 4(197):ra72. doi:10.1126/scisignal.2001843
159. Liu SM, King C (2013) IL-21-producing Th cells in immunity and autoimmunity. Journal of immunology 191(7):3501–3506. doi:10.4049/jimmunol.1301454
160. Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I, Kwok PY, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4(3):e1000041. doi:10.1371/journal.pgen.1000041
161. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8(5):500–508. doi:10.1038/nm0502-500
162. Lohoff M, Mittrucker HW, Prechtl S, Bischof S, Sommer F, Kock S, Ferrick DA, Duncan GS, Gessner A, Mak TW (2002) Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4. Proc Natl Acad Sci USA 99(18):11808–11812. doi:10.1073/pnas.182425099
163. Lubberts E, Joosten LA, van de Loo FA, Schwarzenberger P, Kolls J, van den Berg WB (2002) Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflam Res off J Eur Histamine Res Soc 51(2):102–104
164. Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50(2):650–659. doi:10.1002/art.20001
165. Luthje K, Kallies A, Shimohakamada Y, Belz GT, Light A, Tarlinton DM, Nutt SL (2012) The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat Immunol 13(5):491–498. doi:10.1038/ni.2261
166. Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, Fulcher DA, Tangye SG, Cook MC (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205(7):1551–1557. doi:10.1084/jem.20080218
167. Ma F, Xu S, Liu X, Zhang Q, Xu X, Liu M, Hua M, Li N, Yao H, Cao X (2011) The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma. Nat Immunol 12(9):861–869. doi:10.1038/ni.2073
168. Ma J, Wang R, Fang X, Ding Y, Sun Z (2011) Critical role of TCF-1 in repression of the IL-17 gene. PLoS ONE 6(9):e24768. doi:10.1371/journal.pone.0024768
169. Ma Y, Thornton S, Boivin GP, Hirsh D, Hirsch R, Hirsch E (1998) Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum 41(10):1798–1805. doi:10.1002/1529-0131(199810)41:10<1798::AID-ART11>3.0.CO;2-L
170. Maitra A, Shen F, Hanel W, Mossman K, Tocker J, Swart D, Gaffen SL (2007) Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc Natl Acad Sci USA 104(18):7506–7511. doi:10.1073/pnas.0611589104
171. Male V, Nisoli I, Gascoyne DM, Brady HJ (2012) E4BP4: an unexpected player in the immune response. Trends Immunol 33(2):98–102. doi:10.1016/j.it.2011.10.002
172. Malfait AM, Butler DM, Presky DH, Maini RN, Brennan FM, Feldmann M (1998) Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clin Exp Immunol 111(2):377–383
173. Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9(6):641–649. doi:10.1038/ni.1610
174. Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441(7090):231–234. doi:10.1038/nature04754
175. Marie JC, Letterio JJ, Gavin M, Rudensky AY (2005) TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+ CD25+ regulatory T cells. J Exp Med 201(7):1061–1067. doi:10.1084/jem.20042276
176. Marijnissen RJ, Koenders MI, Smeets RL, Stappers MH, Nickerson-Nutter C, Joosten LA, Boots AM, van den Berg WB (2011) Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation. Arthritis Rheum 63(10):2939–2948. doi:10.1002/art.30469
177. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787–798. doi:10.1016/j.immuni.2009.09.014
178. Mathur AN, Chang HC, Zisoulis DG, Kapur R, Belladonna ML, Kansas GS, Kaplan MH (2006) T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood 108(5):1595–1601. doi:10.1182/blood-2006-04-015016
179. Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O’Malley JT, Kapur R, Levy DE, Kansas GS, Kaplan MH (2007) Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178(8):4901–4907
180. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397. doi:10.1038/ni1539
181. Medvedev A, Chistokhina A, Hirose T, Jetten AM (1997) Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene. Genomics 46(1):93–102. doi:10.1006/geno.1997.4980
182. Mellett M, Atzei P, Horgan A, Hams E, Floss T, Wurst W, Fallon PG, Moynagh PN (2012) Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia. Nat Commun 3:1119. doi:10.1038/ncomms2127
183. Meng G, Zhang F, Fuss I, Kitani A, Strober W (2009) A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30(6):860–874. doi:10.1016/j.immuni.2009.04.012
184. Merkenschlager M, Wilson CB (2008) RNAi and chromatin in T cell development and function. Curr Opin Immunol 20(2):131–138. doi:10.1016/j.coi.2008.03.013
185. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O’Shea J, Holland SM, Paul WE, Douek DC (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452(7188):773–776. doi:10.1038/nature06764
186. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448(7157):1058–1062. doi:10.1038/nature06096
187. Mohawk JA, Green CB, Takahashi JS (2012) and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445–462. doi:10.1146/annurev-neuro-060909-153128
188. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, Olivenstein R, Elias J, Chakir J (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108(3):430–438. doi:10.1067/mai.2001.117929
189. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173. doi:10.1146/annurev.iy.07.040189.001045
190. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317(5835):256–260. doi:10.1126/science.1145697
191. Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202(2):261–269. doi:10.1084/jem.20050678
192. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198(12):1951–1957. doi:10.1084/jem.20030896
193. Murphy E, Shibuya K, Hosken N, Openshaw P, Maino V, Davis K, Murphy K, O’Garra A (1996) Reversibility of T helper 1 and 2 populations is lost after long-term stimulation. J Exp Med 183(3):901–913
194. Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL (2011) Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol 187(5):2213–2221. doi:10.4049/jimmunol.1003952
195. Mycko MP, Cichalewska M, Machlanska A, Cwiklinska H, Mariasiewicz M, Selmaj KW (2012) MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination. Proc Natl Acad Sci USA 109(20):E1248–1257. doi:10.1073/pnas.1114325109
196. Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M, Iwakura Y (2002) Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17(3):375–387
197. Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6(5):369–381. doi:10.1038/nrc1881
198. Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman DR, Taniuchi I (2007) Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer. J Exp Med 204(8):1749–1755. doi:10.1084/jem.20062456
199. Neurath MF, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, Mizoguchi A, Mizoguchi E, Mudter J, Galle PR, Bhan A, Autschbach F, Sullivan BM, Szabo SJ, Glimcher LH, Blumberg RS (2002) The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn’s disease. J Exp Med 195(9):1129–1143
200. Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Hashimoto J, Azuma J, Kishimoto T (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50(6):1761–1769. doi:10.1002/art.20303
201. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, Ramon M, Bergman R, Krueger JG, Guttman-Yassky E (2009) IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 123(6):1244–1252, e1242. doi:10.1016/j.jaci.2009.03.041
202. Novatchkova M, Leibbrandt A, Werzowa J, Neubuser A, Eisenhaber F (2003) The STIR-domain superfamily in signal transduction, development and immunity. Trends Biochem Sci 28(5):226–229. doi:10.1016/S0968-0004(03)00067-7
203. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448(7152):480–483. doi:10.1038/nature05969
204. Oganesyan G, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, Perry A, Cheng G (2006) Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439(7073):208–211. doi:10.1038/nature04374
205. Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y (2004) Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol 110(1):55–62. doi:10.1016/j.clim.2003.09.013
206. Okuda Y, Sakoda S, Bernard CC, Fujimura H, Saeki Y, Kishimoto T, Yanagihara T (1998) IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 10(5):703–708
207. Oliver JA, Stolberg VR, Chensue SW, King PD (2012) IL-4 acts as a potent stimulator of IFN-gamma expression in CD8 + T cells through STAT6-dependent and independent induction of Eomesodermin and T-bet. Cytokine 57(1):191–199. doi:10.1016/j.cyto.2011.10.006
208. Onishi RM, Park SJ, Hanel W, Ho AW, Maitra A, Gaffen SL (2010) SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction. J Biol Chem 285(43):32751–32759. doi:10.1074/jbc.M110.121418
209. Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S (2007) Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446(7136):685–689. doi:10.1038/nature05673
210. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13(5):715–725
211. Ouyang W (2010) Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease. Cytokine Growth Factor Rev 21(6):435–441. doi:10.1016/j.cytogfr.2010.10.007
212. Owyang AM, Zaph C, Wilson EH, Guild KJ, McClanahan T, Miller HR, Cua DJ, Goldschmidt M, Hunter CA, Kastelein RA, Artis D (2006) Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med 203(4):843–849. doi:10.1084/jem.20051496
213. Pan G, French D, Mao W, Maruoka M, Risser P, Lee J, Foster J, Aggarwal S, Nicholes K, Guillet S, Schow P, Gurney AL (2001) Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice. J Immunol 167(11):6559–6567
214. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, Aras G, Li J, Russell CB, Thompson EH, Baumgartner S (2012) Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 366(13):1181–1189. doi:10.1056/NEJMoa1109017
215. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133–1141. doi:10.1038/ni1261
216. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D (2000) Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408(6808):57–63. doi:10.1038/35040504
217. Pennino D, Bhavsar PK, Effner R, Avitabile S, Venn P, Quaranta M, Marzaioli V, Cifuentes L, Durham SR, Cavani A, Eyerich K, Chung KF, Schmidt-Weber CB, Eyerich S (2013) IL-22 suppresses IFN-gamma-mediated lung inflammation in asthmatic patients. J Allergy Clin Immunol 131(2):562–570. doi:10.1016/j.jaci.2012.09.036
218. Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M, Lehr HA, Hirth S, Weigmann B, Wirtz S, Ouyang W, Neurath MF, Becker C (2009) STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 206(7):1465–1472. doi:10.1084/jem.20082683
219. Pisitkun P, Ha HL, Wang H, Claudio E, Tivy CC, Zhou H, Mayadas TN, Illei GG, Siebenlist U (2012) Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity 37(6):1104–1115. doi:10.1016/j.immuni.2012.08.014
220. Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J, Kordula T, Zhang QW, Vallance B, Swaidani S, Aronica M, Tuohy VK, Hamilton T, Li X (2007) The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol 8(3):247–256. doi:10.1038/ni1439
221. Qin H, Wang L, Feng T, Elson CO, Niyongere SA, Lee SJ, Reynolds SL, Weaver CT, Roarty K, Serra R, Benveniste EN, Cong Y (2009) TGF-beta promotes Th17 cell development through inhibition of SOCS3. Journal of immunology 183(1):97–105. doi:10.4049/jimmunol.0801986
222. Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, Jallal B, Yao Y, Shi Y, Qian Y (2012) TRAF6 dependent Act1 phosphorylation by the IKK-related kinases suppresses IL-17-induced NF-kappaB activation. Mol Cell Biol. doi: 10.1128/MCB.00268-12
223. Qui HZ, Hagymasi AT, Bandyopadhyay S, St Rose MC, Ramanarasimhaiah R, Menoret A, Mittler RS, Gordon SM, Reiner SL, Vella AT, Adler AJ (2011) CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol 187(7):3555–3564. doi:10.4049/jimmunol.1101244
224. Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J, Hackney J, Kim J, Zhou M, Lai J, Modrusan Z, Sai T, Lee W, Xu M, Caplazi P, Diehl L, de Voss J, Balazs M, Gonzalez L Jr, Singh H, Ouyang W, Pappu R (2011) IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol 12(12):1159–1166. doi:10.1038/ni.2156
225. Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (2002) Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression. J Exp Med 195(8):1003–1012
226. Renner ED, Rylaarsdam S, Anover-Sombke S, Rack AL, Reichenbach J, Carey JC, Zhu Q, Jansson AF, Barboza J, Schimke LF, Leppert MF, Getz MM, Seger RA, Hill HR, Belohradsky BH, Torgerson TR, Ochs HD (2008) Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122(1):181–187. doi:10.1016/j.jaci.2008.04.037
227. Reynolds JM, Martinez GJ, Nallaparaju KC, Chang SH, Wang YH, Dong C (2012) Cutting edge: regulation of intestinal inflammation and barrier function by IL-17C. J Immunol 189(9):4226–4230. doi:10.4049/jimmunol.1103014
228. Rickel EA, Siegel LA, Yoon BR, Rottman JB, Kugler DG, Swart DA, Anders PM, Tocker JE, Comeau MR, Budelsky AL (2008) Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J Immunol 181(6):4299–4310
229. Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A (2011) IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. Journal of immunology 186(3):1495–1502. doi:10.4049/jimmunol.1001001
230. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316(5824):608–611. doi:10.1126/science.1139253
231. Ron D, Fuchs Y, Chorev DS (2008) Know thy Sef: a novel class of feedback antagonists of receptor tyrosine kinase signaling. Int J Biochem Cell Biol 40(10):2040–2052. doi:10.1016/j.biocel.2008.03.013
232. Rouvier E, Luciani MF, Mattei MG, Denizot F, Golstein P (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 150(12):5445–5456
233. Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, Komatsu R, Miura N, Adachi Y, Ohno N, Shibuya K, Yamamoto N, Kawakami K, Yamasaki S, Saito T, Akira S, Iwakura Y (2010) Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32(5):681–691. doi:10.1016/j.immuni.2010.05.001
234. Saleh A, Shan L, Halayko AJ, Kung S, Gounni AS (2009) Critical role for STAT3 in IL-17A-mediated CCL11 expression in human airway smooth muscle cells. J Immunol 182(6):3357–3365. doi:10.4049/jimmunol.0801882
235. Samoilova EB, Horton JL, Hilliard B, Liu TS, Chen Y (1998) IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 161(12):6480–6486
236. Sarkar S, Zhou X, Justa S, Bommireddy SR (2013) Interleukin-22 reduces the severity of collagen-induced arthritis in association with increased levels of interleukin-10. Arthritis Rheum 65(4):960–971. doi:10.1002/art.37849
237. Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, Lohse P, Goke B, Brand S (2008) Linking genetic susceptibility to Crohn’s disease with Th17 cell function: IL-22 serum levels are increased in Crohn’s disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis 14(2):204–212. doi:10.1002/ibd.20315
238. Schnyder B, Lima C, Schnyder-Candrian S (2010) Interleukin-22 is a negative regulator of the allergic response. Cytokine 50(2):220–227. doi:10.1016/j.cyto.2010.02.003
239. Schulz SM, Kohler G, Schutze N, Knauer J, Straubinger RK, Chackerian AA, Witte E, Wolk K, Sabat R, Iwakura Y, Holscher C, Muller U, Kastelein RA, Alber G (2008) Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. Journal of immunology 181(11):7891–7901
240. Schwandner R, Yamaguchi K, Cao Z (2000) Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J Exp Med 191(7):1233–1240
241. Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jurgens M, Schmechel S, Konrad A, Goke B, Ochsenkuhn T, Muller-Myhsok B, Lohse P, Brand S (2008) Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis 14(4):437–445. doi:10.1002/ibd.20339
242. Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, Tomita S, Imura J, Shiratori K, Chiba T, Fujimori T (2010) Involvement of the IL-22/REG Ialpha axis in ulcerative colitis. Lab Invest J Tech Methods pathol 90(3):496–505. doi:10.1038/labinvest.2009.147
243. Serada S, Fujimoto M, Mihara M, Koike N, Ohsugi Y, Nomura S, Yoshida H, Nishikawa T, Terabe F, Ohkawara T, Takahashi T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105(26):9041–9046. doi:10.1073/pnas.0802218105
244. Shaw PJ, Lukens JR, Burns S, Chi H, McGargill MA, Kanneganti TD (2010) Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. J Immunol 184(9):4610–4614. doi:10.4049/jimmunol.1000217
245. Shen F, Li N, Gade P, Kalvakolanu DV, Weibley T, Doble B, Woodgett JR, Wood TD, Gaffen SL (2009) IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain. Science signaling 2(59):ra8. doi:10.1126/scisignal.2000066
246. Shi P, Zhu S, Lin Y, Liu Y, Liu Y, Chen Z, Shi Y, Qian Y (2011) Persistent stimulation with interleukin-17 desensitizes cells through SCFbeta-TrCP-mediated degradation of Act1. Sci Signal 4(197):ra73. doi:10.1126/scisignal.2001653
247. Smith KM, Guerau-de-Arellano M, Costinean S, Williams JL, Bottoni A, Mavrikis Cox G, Satoskar AR, Croce CM, Racke MK, Lovett-Racke AE, Whitacre CC (2012) miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. Journal of immunology 189(4):1567–1576. doi:10.4049/jimmunol.1103171
248. Sonder SU, Saret S, Tang W, Sturdevant DE, Porcella SF, Siebenlist U (2011) IL-17-induced NF-kappaB activation via CIKS/Act1: physiologic significance and signaling mechanisms. J Biol Chem 286(15):12881–12890. doi:10.1074/jbc.M110.199547
249. Sonderegger I, Kisielow J, Meier R, King C, Kopf M (2008) IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol 38(7):1833–1838. doi:10.1002/eji.200838511
250. Song X, Gao H, Lin Y, Yao Y, Zhu S, Wang J, Liu Y, Yao X, Meng G, Shen N, Shi Y, Iwakura Y, Qian Y (2014) Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity 40(1):140–152. doi:10.1016/j.immuni.2013.11.018
251. Song X, Qian Y (2013) The activation and regulation of IL-17 receptor mediated signaling. Cytokine 62(2):175–182. doi:10.1016/j.cyto.2013.03.014
252. Song X, Qian Y (2013) IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases. Cell Signal 25(12):2335–2347. doi:10.1016/j.cellsig.2013.07.021
253. Song X, Zhu S, Shi P, Liu Y, Shi Y, Levin SD, Qian Y (2011) IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nat Immunol 12(12):1151–1158. doi:10.1038/ni.2155
254. Staal FJ, Luis TC, Tiemessen MM (2008) WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 8(8):581–593. doi:10.1038/nri2360
255. Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, Matloubian M, Blelloch R, Ansel KM (2011) MicroRNA-29 regulates T-box transcription factors and interferon-gamma production in helper T cells. Immunity 35(2):169–181. doi:10.1016/j.immuni.2011.07.009
256. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Huffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mossner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Stahle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42(11):985–990. doi:10.1038/ng.694
257. Stromnes IM, Goverman JM (2006) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1(4):1810–1819. doi:10.1038/nprot.2006.285
258. Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O’Shea JJ, Hennighausen L, Ernst M, Hunter CA (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the nervous system. Nat Immunol 7(9):937–945. doi:10.1038/ni1376
259. Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, Fujiyama Y, Andoh A (2010) The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol 160(3):386–393. doi:10.1111/j.1365-2249.2010.04093.x
260. Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, Blumberg RS, Xavier RJ, Mizoguchi A (2008) IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 118(2):534–544. doi:10.1172/JCI33194
261. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204(8):1775–1785. doi:10.1084/jem.20070602
262. Sun D, Novotny M, Bulek K, Liu C, Li X, Hamilton T (2011) Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF). Nat Immunol 12(9):853–860. doi:10.1038/ni.2081
263. Suto A, Kashiwakuma D, Kagami S, Hirose K, Watanabe N, Yokote K, Saito Y, Nakayama T, Grusby MJ, Iwamoto I, Nakajima H (2008) Development and characterization of IL-21-producing CD4 + T cells. J Exp Med 205(6):1369–1379. doi:10.1084/jem.20072057
264. Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC (2006) A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 203(7):1685–1691. doi:10.1084/jem.20060285
265. Swaidani S, Bulek K, Kang Z, Liu C, Lu Y, Yin W, Aronica M, Li X (2009) The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation. J Immunol 182(3):1631–1640
266. Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185(5):817–824
267. Takahashi K, Hirose K, Kawashima S, Niwa Y, Wakashin H, Iwata A, Tokoyoda K, Renauld JC, Iwamoto I, Nakayama T, Nakajima H (2011) IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation. The Journal of allergy and clinical immunology 128(5):1067–1076, e1061–1066. doi:10.1016/j.jaci.2011.06.018
268. Tamachi T, Maezawa Y, Ikeda K, Kagami S, Hatano M, Seto Y, Suto A, Suzuki K, Watanabe N, Saito Y, Tokuhisa T, Iwamoto I, Nakajima H (2006) IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J Allergy Clin Immunol 118(3):606–614. doi:10.1016/j.jaci.2006.04.051
269. Teunissen MB, Koomen CW, de Malefyt Waal R, Wierenga EA, Bos JD (1998) Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 111(4):645–649. doi:10.1046/j.1523-1747.1998.00347.x
270. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K (2007) Regulation of the germinal center response by microRNA-155. Science 316(5824):604–608. doi:10.1126/science.1141229
271. Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, Fang W, Xiong B, Wan Y, Dong C (2012) A protective role by interleukin-17F in colon tumorigenesis. PLoS ONE 7(4):e34959. doi:10.1371/journal.pone.0034959
272. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, Galon J (2011) Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71(4):1263–1271. doi:10.1158/0008-5472.CAN-10-2907
273. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 177(1):36–39
274. Tran EH, Prince EN, Owens T (2000) IFN-gamma shapes immune invasion of the nervous system via regulation of chemokines. J Immunol 164(5):2759–2768
275. Tschopp J, Martinon F, Burns K (2003) NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 4(2):95–104. doi:10.1038/nrm1019
276. Tseng PH, Matsuzawa A, Zhang W, Mino T, Vignali DA, Karin M (2009) Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nat Immunol 11(1):70–75. doi:10.1038/ni.1819
277. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin-17 production in nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172(1):146–155. doi:10.2353/ajpath.2008.070690
278. Van Belle AB, de Heusch M, Lemaire MM, Hendrickx E, Warnier G, Dunussi-Joannopoulos K, Fouser LA, Renauld JC, Dumoutier L (2012) IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice. J Immunol 188(1):462–469. doi:10.4049/jimmunol.1102224
279. Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278. doi:10.1146/annurev.iy.08.040190.001345
280. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453(7191):106–109. doi:10.1038/nature06881
281. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179–189. doi:10.1016/j.immuni.2006.01.001
282. Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006) Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7(11):1151–1156. doi:10.1038/ni1391
283. Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupe P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9(6):650–657. doi:10.1038/ni.1613
284. Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ (2009) Identification of IL-17-producing FOXP3 + regulatory T cells in humans. Proc Natl Acad Sci USA 106(12):4793–4798. doi:10.1073/pnas.0900408106
285. Wang C, Wu L, Bulek K, Martin BN, Zepp JA, Kang Z, Liu C, Herjan T, Misra S, Carman JA, Gao J, Dongre A, Han S, Bunting KD, Ko JS, Xiao H, Kuchroo VK, Ouyang W, Li X (2013) The psoriasis-associated D10 N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. Nat Immunol 14(1):72–81. doi:10.1038/ni.2479
286. Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, Sleiman PM, Imielinski M, Glessner J, Hou C, Wilson DC, Walters T, Kim C, Frackelton EC, Lionetti P, Barabino A, Van Limbergen J, Guthery S, Denson L, Piccoli D, Li M, Dubinsky M, Silverberg M, Griffiths A, Grant SF, Satsangi J, Baldassano R, Hakonarson H (2009) Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn disease. Am J Hum Genet 84(3):399–405. doi:10.1016/j.ajhg.2009.01.026
287. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206(7):1457–1464. doi:10.1084/jem.20090207
288. Wang L, Yi T, Zhang W, Pardoll DM, Yu H (2010) IL-17 enhances tumor development in carcinogen-induced skin cancer. Cancer Res 70(24):10112–10120. doi:10.1158/0008-5472.CAN-10-0775
289. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, Schones DE, Peng W, Sun HW, Paul WE, O’Shea JJ, Zhao K (2009) Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4 + T cells. Immunity 30(1):155–167. doi:10.1016/j.immuni.2008.12.009
290. Wilson CB, Rowell E, Sekimata M (2009) Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9(2):91–105. doi:10.1038/nri2487
291. Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, de Waal Malefyt R (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957. doi:10.1038/ni1497
292. Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, Vom Baur E, Witte K, Warszawska K, Philipp S, Johnson-Leger C, Volk HD, Sterry W, Sabat R (2009) IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med 87(5):523–536. doi:10.1007/s00109-009-0457-0
293. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21(2):241–254. doi:10.1016/j.immuni.2004.07.007
294. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36(5):1309–1323. doi:10.1002/eji.200535503
295. Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, Tomkinson KN, Fitz LJ, Wolfman NM, Collins M, Dunussi-Joannopoulos K, Chatterjee-Kishore M, Carreno BM (2008) The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. Journal of immunology 181(4):2799–2805
296. Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A, Kuchroo VK (2013) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496(7446):513–517. doi:10.1038/nature11984
297. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15(9):1016–1022. doi:10.1038/nm.2015
298. Xiao S, Jin H, Korn T, Liu SM, Oukka M, Lim B, Kuchroo VK (2008) Retinoic acid increases Foxp3 + regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 181(4):2277–2284
299. Xie P, Stunz LL, Larison KD, Yang B, Bishop GA (2007) Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs. Immunity 27(2):253–267. doi:10.1016/j.immuni.2007.07.012
300. Xu L, Kitani A, Fuss I, Strober W (2007) Cutting edge: regulatory T cells induce CD4 + CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J immunol 178(11):6725–6729
301. Xu X, Weiss ID, HZ H, Singh SP, Wynn TA, Wilson MS, Farber JM (2014) Conventional NK Cells Can Produce IL-22 and Promote Host Defense in Klebsiella pneumoniae Pneumonia. J Immunol 192(4):1778–1786. doi:10.4049/jimmunol.1300039
302. Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Tsuno NH, Takahashi K, Yamamoto K (2007) IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J Immunol 179(10):7128–7136
303. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454(7202):350–352. doi:10.1038/nature07021
304. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C (2008) Regulation of inflammatory responses by IL-17F. J Exp Med 205(5):1063–1075. doi:10.1084/jem.20071978
305. Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, Feng XH, Jetten AM, Dong C (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1):44–56. doi:10.1016/j.immuni.2008.05.007
306. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282(13):9358–9363. doi:10.1074/jbc.C600321200
307. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28(1):29–39. doi:10.1016/j.immuni.2007.11.016
308. Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O’Shea JJ, Laurence A (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12(3):247–254. doi:10.1038/ni.1995
309. Yang Y, Xu J, Niu Y, Bromberg JS, Ding Y (2008) T-bet and eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17. Journal of immunology 181(12):8700–8710
310. Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X, Liao YH (2012) MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 7(10):e46082. doi:10.1371/journal.pone.0046082
311. Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI, Spriggs MK (1995) Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3(6):811–821
312. Yu Q, Sharma A, Ghosh A, Sen JM (2011) T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. Journal of immunology 186(7):3946–3952. doi:10.4049/jimmunol.1003497
313. Yu X, Rollins D, Ruhn KA, Stubblefield JJ, Green CB, Kashiwada M, Rothman PB, Takahashi JS, Hooper LV (2013) TH17 cell differentiation is regulated by the circadian clock. Science 342(6159):727–730. doi:10.1126/science.1243884
314. Zaph C, Du Y, Saenz SA, Nair MG, Perrigoue JG, Taylor BC, Troy AE, Kobuley DE, Kastelein RA, Cua DJ, Yu Y, Artis D (2008) Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med 205(10):2191–2198. doi:10.1084/jem.20080720
315. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29(6):947–957. doi:10.1016/j.immuni.2008.11.003
316. Zepp JA, Liu C, Qian W, Wu L, Gulen MF, Kang Z, Li X (2012) Cutting Edge: TNF Receptor-Associated Factor 4 Restricts IL-17-Mediated Pathology and Signaling Processes. J Immunol 189(1):33–37. doi:10.4049/jimmunol.1200470
317. Zhang F, Meng G, Strober W (2008) Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol 9(11):1297–1306. doi:10.1038/ni.1663
318. Zhang GX, Gran B, Yu S, Li J, Siglienti I, Chen X, Kamoun M, Rostami A (2003) Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the nervous system. J Immunol 170(4):2153–2160
319. Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, Wu C, Li SP, Zheng L (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50(5):980–989. doi:10.1016/j.jhep.2008.12.033
320. Zhang Y, Wang X, Zhong M, Zhang M, Suo Q, Lv K (2013) MicroRNA let-7a ameliorates con A-induced hepatitis by inhibiting IL-6-dependent Th17 cell differentiation. J Clin Immunol 33(3):630–639. doi:10.1007/s10875-012-9840-7
321. Zhang Z, Kyttaris VC, Tsokos GC (2009) The role of IL-23/IL-17 axis in lupus nephritis. J Immunol 183(5):3160–3169. doi:10.4049/jimmunol.0900385
322. Zhao A, Urban JF Jr, Sun R, Stiltz J, Morimoto M, Notari L, Madden KB, Yang Z, Grinchuk V, Ramalingam TR, Wynn TA, Shea-Donohue T (2010) Critical role of IL-25 in nematode infection-induced alterations in intestinal function. Journal of immunology 185(11):6921–6929. doi:10.4049/jimmunol.1000450
323. Zhao C, Dahlman-Wright K (2010) Liver X receptor in cholesterol metabolism. J Endocrinol 204(3):233–240. doi:10.1677/JOE-09-0271
324. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445(7128):648–651. doi:10.1038/nature05505
325. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14(3):282–289. doi:10.1038/nm1720
326. Zhong B, Liu X, Wang X, Chang SH, Wang A, Reynolds JM, Dong C (2012) Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. Nat Immunol 13(11):1110–1117. doi:10.1038/ni.2427
327. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8(9):967–974. doi:10.1038/ni1488
328. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453(7192):236–240. doi:10.1038/nature06878
329. Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33(2):229–240. doi:10.1016/j.immuni.2010.08.002
330. Zhou Y, Toh ML, Zrioual S, Miossec P (2007) IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. Cytokine 38(3):157–164. doi:10.1016/j.cyto.2007.06.002
331. Zhu J, Davidson TS, Wei G, Jankovic D, Cui K, Schones DE, Guo L, Zhao K, Shevach EM, Paul WE (2009) Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103 + inducible regulatory T cells. J Exp Med 206(2):329–341. doi:10.1084/jem.20081666
332. Zhu J, Guo L, Min B, Watson CJ, Hu-Li J, Young HA, Tsichlis PN, Paul WE (2002) Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16(5):733–744
333. Zhu S, Pan W, Qian Y (2013) MicroRNA in immunity and autoimmunity. J Mol Med 91(9):1039–1050. doi:10.1007/s00109-013-1043-z
334. Zhu S, Pan W, Shi P, Gao H, Zhao F, Song X, Liu Y, Zhao L, Li X, Shi Y, Qian Y (2010) Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling. J Exp Med 207(12):2647–2662. doi:10.1084/jem.20100703
335. Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, Liang D, He D, Wang H, Liu W, Shi Y, Harley JB, Shen N, Qian Y (2012) The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha. Nat Med 18(7):1077–1086. doi:10.1038/nm.2815
336. Zhu S, Qian Y (2012) IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci 122(11):487–511. doi:10.1042/CS20110496
337. Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J immunol 164(5):2832–2838