Th17 cells in autoimmune diseases

Frontiers of Medicine

Volumn 9, Issue 1, 2015, Pages 10-19

  Han, Lei ^a   Yang, Jing ^b   Wang, Xiuwen ^a   Li, Dan ^b   Lv, Ling ^a   Li, Bin ^b  

^a FUDAN UNIVERSITY   (China)

^b INSTITUTE PASTEUR OF SHANGHAI   (China)

Author keywords

autoimmune diseases; IL 17; inhibitors; posttranslational modification; ROR t; Th17 cells

Indexed keywords

CYTOKINE;

AUTOIMMUNE DISEASES; DRUG EFFECTS; HUMAN; IMMUNOLOGY; INFLAMMATION; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY; PROTEIN PROCESSING; TH17 CELL;

AUTOIMMUNE DISEASES; CYTOKINES; HUMANS; INFLAMMATION; MOLECULAR TARGETED THERAPY; PROTEIN PROCESSING, POST-TRANSLATIONAL; TH17 CELLS;

EID: 84941023497     PISSN: 20950217     EISSN: 20950225     Source Type: Journal    
DOI: 10.1007/s11684-015-0388-9     Document Type: Review

References (117)

1. 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. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003; 421(6924): 744–748
2. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003; 198(12): 1951–1957
3. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005; 6(11): 1133–1141
4. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 2008; 28(4): 454–467
5. Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT. Transforming growth factor-beta induces development of the T(H) 17 lineage. Nature 2006; 441(7090): 231–234
6. Bedoya SK, Lam B, Lau K, Larkin J 3rd. Th17 cells in immunity and autoimmunity. Clin Dev Immunol 2013; 2013: 986789
7. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441(7090): 235–238
8. Wei L, Laurence A, Elias KM, O’Shea JJ. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 2007; 282(48): 34605–34610
9. Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature 2008; 453(7198): 1051–1057
10. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 2007; 8(9): 942–949
11. Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E, Soumelis V. A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 2008; 9(6): 650–657
12. Manel N, Unutmaz D, Littman DR. The differentiation of human T (H)-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORgt. Nat Immunol 2008; 9(6): 641–649
13. + T helper cells. Cell 2006; 126(6): 1121–1133
14. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T. Foxp3 inhibits RORgt-mediated IL-17A mRNA transcription through direct interaction with RORgt. J Biol Chem 2008; 283(25): 17003–17008
15. 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. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORg. Immunity 2008; 28(1): 29–39
16. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 2007; 282(13): 9358–9363
17. Brüstle A, Heink S, Huber M, Rosenplänter C, Stadelmann C, Yu P, Arpaia E, Mak TW, Kamradt T, Lohoff M. The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 2007; 8(9): 958–966
18. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 2008; 453(7191): 65–71
19. Liu C, Qian W, Qian Y, Giltiay NV, Lu Y, Swaidani S, Misra S, Deng L, Chen ZJ, Li X. Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci Signal 2009; 2(92): ra63
20. Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, Wu C, Kleinewietfeld M, Kunder S, Hafler DA, Sobel RA, Regev A, Kuchroo VK. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol 2012; 13(10): 991–999
21. Benedetti G, Miossec P. Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol 2014; 44(2): 339–347
22. Metawi SA, Abbas D, Kamal MM, Ibrahim MK. Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. Clin Rheumatol 2011; 30(9): 1201–1207
23. Suurmond J, Dorjée AL, Boon MR, Knol EF, Huizinga TW, Toes RE, Schuerwegh AJ. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive andnegative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther 2011; 13(5): R150
24. Park JS, Park MK, Lee SY, Oh HJ, Lim MA, Cho WT, Kim EK, Ju JH, Park YW, Park SH, Cho ML, Kim HY. TWEAK promotes the production of interleukin-17 in rheumatoid arthritis. Cytokine 2012; 60(1): 143–149
25. Lubberts E, Koenders MI, van den Berg WB. The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther 2005; 7(1): 29–37
26. Chao CC, Chen SJ, Adamopoulos IE, Davis N, Hong K, Vu A, Kwan S, Fayadat-Dilman L, Asio A, Bowman EP. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity 2011; 44(3): 243–252
27. Kellner H. Targeting interleukin-17 in patients with active rheumatoid arthritis: rationale and clinical potential. Ther Adv Musculoskelet Dis; 5(3): 141–152
28. Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis 2013; 72(Suppl 2): ii116–ii123
29. Jain M, Attur M, Furer V, Todd J, Ramirez R, Lock M, Lu QA, Abramson SB, Greenberg JD. Increased plasma IL-17F levels in rheumatoid arthritis patients are responsive to methotrexate, anti-TNF, and T Cell costimulatory modulation. Inflammation 2014 Sep 21. [Epub ahead of print]
30. + Th cells that cause autoimmune arthritis. J Exp Med 2007; 204(1): 41–47
31. Leipe J, Schramm MA, Prots I, Schulze-Koops H, Skapenko A. Increased Th17 cell frequency and poor clinical outcome in rheumatoid arthritis are associated with a genetic variant in the IL4R gene, rs1805010. Arthritis Rheum (Munch) 2014; 66(5): 1165–1175
32. Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009; 60(6): 1647–1656
33. van Hamburg JP, Asmawidjaja PS, Davelaar N, Mus AM, Colin EM, Hazes JM, Dolhain RJ, Lubberts E. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum 2011; 63(1): 73–83
34. Zhang L, Li YG, Li YH, Qi L, Liu XG, Yuan CZ, Hu NW, Ma DX, Li ZF, Yang Q, Li W, Li JM. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS ONE 2012; 7(4): e31000
35. van Hamburg JP, Corneth OB, Paulissen SM, Davelaar N, Asmawidjaja PS, Mus AM, Lubberts E. IL-17/Th17 mediated synovial inflammation is IL-22 independent. Ann Rheum Dis 2013; 72(10): 1700–1707
36. Kim J, Kang S, Kim J, Kwon G, Koo S. Elevated levels of T helper 17 cells are associated with disease activity in patients with rheumatoid arthritis. Ann Lab Med 2013; 33(1): 52–59
37. Church LD, Filer AD, Hidalgo E, Howlett KA, Thomas AM, Rapecki S, Scheel-Toellner D, Buckley CD, Raza K. Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-α co-expression, but little interleukin-22 and interleukin-23R expression. Arthritis Res Ther 2010; 12(5): R184
38. Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, Evans JG, Cimaz R, Bajaj-Elliott M, Wedderburn LR. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci USA 2010; 107(33): 14751–14756
39. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 2006; 203(12): 2673–2682
40. Hickman-Brecks CL, Racz JL, Meyer DM, LaBranche TP, Allen PM. Th17 cells can provide B cell help in autoantibody induced arthritis. J Autoimmun 2011; 36(1): 65–75
41. + T cells into TH17 cells in autoimmune arthritis. Nat Med 2014; 20(1): 62–68
42. Shlomchik MJ, Craft JE, Mamula MJ. From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 2001; 1(2): 147–153
43. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 2008; 127(3): 385–393
44. Zhao XF, Pan HF, Yuan H, Zhang WH, Li XP, Wang GH, Wu GC, Su H, Pan FM, Li WX, Li LH, Chen GP, Ye DQ. Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep 2010; 37(1): 81–85
45. Cheng F, Guo Z, Xu H, Yan D, Li Q. Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 2009; 68(4): 604–606
46. Vincent FB, Northcott M, Hoi A, Mackay F, Morand EF. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Res Ther 2013; 15(4): R97
47. Amarilyo G, Lourenço EV, Shi FD, La Cava A. IL-17 promotes murine lupus. J Immunol 2014; 193(2): 540–543
48. + Treg cells decrease in patients with lupus nephritis. Rheumatol Int 2012; 32(4): 949–958
49. + CD4-CD8-double-negative T cells and contracts regulatory T cells in systemic lupus erythematosus. J Immunol 2014; 192(9): 4134–4144
50. Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, Kyttaris VC, Juang YT, Tsokos GC. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol 2008; 181(12): 8761–8766
51. Mizui M, Koga T, Lieberman LA, Beltran J, Yoshida N, Johnson MC, Tisch R, Tsokos GC. IL-2 protects lupus-prone mice from multiple end-organ damage by limiting CD4-CD8-IL-17-producing T cells. J Immunol 2014; 193(5): 2168–2177
52. Shah K, Lee WW, Lee SH, Kim SH, Kang SW, Craft J, Kang I. Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus. Arthritis Res Ther 2010; 12(2): R53
53. Yang XY, Wang HY, Zhao XY, Wang LJ, Lv QH, Wang QQ. Th22, but not Th17 might be a good index to predict the tissue involvement of systemic lupus erythematosus. J Clin Immunol 2013; 33(4): 767–774
54. Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, Wan L, Li M. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum 2009; 60(5): 1472–1483
55. Chen DY, Chen YM, Wen MC, Hsieh TY, Hung WT, Lan JL. The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis. Lupus 2012; 21(13): 1385–1396
56. Dolff S, Bijl M, Huitema MG, Limburg PC, Kallenberg CG, Abdulahad WH. Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus. Clin Immunol 2011; 141(2): 197–204
57. Voulgarelis M, Tzioufas AG. Pathogenetic mechanisms in the initiation and perpetuation of Sjögren’s syndrome. Nat Rev Rheumatol 2010; 6(9): 529–537
58. Jonsson R, Vogelsang P, Volchenkov R, Espinosa A, Wahren-Herlenius M, Appel S. The complexity of Sjögren’s syndrome: novel aspects on pathogenesis. Immunol Lett 2011; 141(1): 1–9
59. Singh N, Cohen PL. The T cell in Sjogren’s syndrome: force majeure, not spectateur. J Autoimmun 2012; 39(3): 229–233
60. Fox RI, Adamson TC 3rd, Fong S, Young C, Howell FV. Characterization of the phenotype and function of lymphocytes infiltrating the salivary gland in patients with primary Sjögren syndrome. Diagn Immunol 1983; 1(3): 233–239
61. Lin X, Tian J, Rui K, Ma KY, Ko KH, Wang S, Lu L. The role of T helper 17 cell subsets in Sjögren’s syndrome: similarities and differences between mouse model and humans. Ann Rheum Dis 2014; 73(7): e43
62. Nguyen CQ, Yin H, Lee BH, Carcamo WC, Chiorini JA, Peck AB. Pathogenic effect of interleukin-17A in induction of Sjögren’s syndrome-like disease using adenovirus-mediated gene transfer. Arthritis Res Ther 2010; 12(6): R220
63. Ciccia F, Guggino G, Rizzo A, Ferrante A, Raimondo S, Giardina A, Dieli F, Campisi G, Alessandro R, Triolo G. Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjögren’s syndrome. Ann Rheum Dis 2012; 71(2): 295–301
64. Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren’s syndrome: findings in humans and mice. Arthritis Rheum 2008; 58(3): 734–743
65. Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol 2008; 181(4): 2898–2906
66. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleukin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. Am J Pathol 2009; 175(3): 1167–1177
67. Fei Y, Zhang W, Lin D, Wu C, Li M, Zhao Y, Zeng X, Zhang F. Clinical parameter and Th17 related to lymphocytes infiltrating degree of labial salivary gland in primary Sjögren’s syndrome. Clin Rheumatol 2014; 33(4): 523–529
68. Youinou P, Pers JO. Disturbance of cytokine networks in Sjögren’s syndrome. Arthritis Res Ther 2011; 13(4): 227
69. Alunno A, Bistoni O, Bartoloni E, Caterbi S, Bigerna B, Tabarrini A, Mannucci R, Falini B, Gerli R. IL-17-producing CD4-CD8-T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary Sjögren’s syndrome. Ann Rheum Dis 2013; 72(2): 286–292
70. Alunno A, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Bigerna B, Pacini R, Beghelli D, Cipriani P, Giacomelli R, Gerli R. CD4(-) CD8(-) T-cells in primary Sjögren’s syndrome: association with the extent of glandular involvement. J Autoimmun 2014; 51: 38–43
71. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28(1): 573–621
72. Di Sabatino A, Biancheri P, Rovedatti L, MacDonald TT, Corazza GR. New pathogenic paradigms in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(2): 368–371
73. Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347(6): 417–429
74. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52(1): 65–70
75. Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jürgens M, Schmechel S, Konrad A, Göke B, Ochsenkühn T, Müller-Myhsok B, Lohse P, Brand S. 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 2008; 14(4): 437–445
76. Zenewicz LA, Antov A, Flavell RA. CD4 T-cell differentiation and inflammatory bowel disease. Trends Mol Med 2009; 15(5): 199–207
77. Feng T, Qin H, Wang L, Benveniste EN, Elson CO, Cong Y. Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol 2011; 186(11): 6313–6318
78. Lees CW, Barrett JC, Parkes M, Satsangi J. New IBD genetics: common pathways with other diseases. Gut 2011; 60(12): 1739–1753
79. + macrophages and decreased IL-17 expression in intestinal mucosa of patients with inflammatory bowel disease strongly correlate with endoscopic response and mucosal healing following infliximab therapy. Inflamm Bowel Dis 2013; 19(4): 729–739
80. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13(1): 3–10
81. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C. Regulation of inflammatory responses by IL-17F. J Exp Med 2008; 205(5): 1063–1075
82. O’Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK, Flavell RA. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 2009; 10(6): 603–609
83. Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls JK. Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis 2006; 12(5): 382–388
84. Troncone E, Marafini I, Pallone F, Monteleone G. Th17 cytokines in inflammatory bowel diseases: discerning the good from the bad. Int Rev Immunol 2013; 32(5–6): 526–533
85. Sarra M, Pallone F, Macdonald TT, Monteleone G. IL-23/IL-17 axis in IBD. Inflamm Bowel Dis 2010; 16(10): 1808–1813
86. Morrison PJ, Bending D, Fouser LA, Wright JF, Stockinger B, Cooke A, Kullberg MC. Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation. Mucosal Immunol 2013; 6(6): 1143–1156
87. Morrison PJ, Ballantyne SJ, Kullberg MC. Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity. Immunology 2011; 133(4): 397–408
88. Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, Wehkamp J, Feagan BG, Yao MD, Karczewski M, Karczewski J, Pezous N, Bek S, Bruin G, Mellgard B, Berger C, Londei M, Bertolino AP, Tougas G, Travis SP; Secukinumab in Crohn’s Disease Study Group. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012; 61(12): 1693–1700
89. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007; 8(9): 913–919
90. Voskuhl RR, Martin R, Bergman C, Dalal M, Ruddle NH, McFarland HF. T helper 1 (Th1) functional phenotype of human myelin basic protein-specific T lymphocytes. Autoimmunity 1993; 15(2): 137–143
91. Kroenke MA, Chensue SW, Segal BM. EAE mediated by a non-IFN-γ/non-IL-17 pathway. Eur J Immunol 2010; 40(8): 2340–2348
92. Jäger A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009; 183(11): 7169–7177
93. Romme Christensen J, Börnsen L, Ratzer R, Piehl F, Khademi M, Olsson T, Sørensen PS, Sellebjerg F. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression. PLoS ONE 2013; 8(3): e57820
94. Tao Y, Zhang X, Chopra M, Kim MJ, Buch KR, Kong D, Jin J, Tang Y, Zhu H, Jewells V, Markovic-Plese S. The role of endogenous IFN-β in the regulation of Th17 responses in patients with relapsing-remitting multiple sclerosis. J Immunol 2014; 192(12): 5610–5617
95. Coquet JM, Middendorp S, van der Horst G, Kind J, Veraar EA, Xiao Y, Jacobs H, Borst J. The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity. Immunity 2013; 38(1): 53–65
96. Haak S, Croxford AL, Kreymborg K, Heppner FL, Pouly S, Becher B, Waisman A. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest 2009; 119(1): 61–69
97. Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B. IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 2007; 179(12): 8098–8104
98. Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol 2008; 38(7): 1833–1838
99. Codarri L, Gyülvészi G, Tosevski V, Hesske L, Fontana A, Magnenat L, Suter T, Becher B. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011; 12(6): 560–567
100. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011; 12(6): 568–575
101. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 2013; 496(7446): 518–522
102. Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 2009; 10(5): 514–523
103. Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012; 181(1): 8–18
104. Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, Dooley LT, Lebwohl M; CNTO 1275 Psoriasis Study Group. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007; 356(6): 580–592
105. Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P; Ustekinumab Crohn’s Disease Study Group. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology 2008; 135(4): 1130–1141
106. Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group, Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group, Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010; 2(52): 52ra72
107. Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, Sloan-Lancaster J. LY2439821, a humanized antiinterleukin-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 2010; 62(4): 929–939
108. Huh JR, Littman DR. Small molecule inhibitors of RORγt: targeting Th17 cells and other applications. Eur J Immunol 2012; 42(9): 2232–2237
109. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, Littman DR. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature 2011; 472(7344): 486–490
110. Solt LA, Kumar N, Nuhant P, Wang Y, Lauer JL, Liu J, Istrate MA, Kamenecka TM, Roush WR, Vidović D, Schürer SC, Xu J, Wagoner G, Drew PD, Griffin PR, Burris TP. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 2011; 472(7344): 491–494
111. Xu T, Wang X, Zhong B, Nurieva RI, Ding S, Dong C. Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgt protein. J Biol Chem 2011; 286(26): 22707–22710
112. Cascão R, Vidal B, Raquel H, Neves-Costa A, Figueiredo N, Gupta V, Fonseca JE, Moita LF. Effective treatment of rat adjuvantinduced arthritis by celastrol. Autoimmun Rev 2012; 11(12): 856–862
113. Xiao S, Yosef N, Yang J, Wang Y, Zhou L, Zhu C, Wu C, Baloglu E, Schmidt D, Ramesh R, Lobera M, Sundrud MS, Tsai PY, Xiang Z, Wang J, Xu Y, Lin X, Kretschmer K, Rahl PB, Young RA, Zhong Z, Hafler DA, Regev A, Ghosh S, Marson A, Kuchroo VK. Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity 2014; 40(4): 477–489
114. Xie L, Chen J, McMickle A, Awar N, Nady S, Sredni B, Drew PD, Yu S. The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis. J Neuroimmunol 2014; 273(1–2): 31–41
115. Zhong B, Liu X, Wang X, Chang SH, Liu X, Wang A, Reynolds JM, Dong C. Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. Nat Immunol 2012; 13(11): 1110–1117
116. Han L, Yang J, Wang X, Wu Q, Yin S, Li Z, Zhang J, Xing Y, Chen Z, Tsun A, Li D, Piccioni M, Zhang Y, Guo Q, Jiang L, Bao L, Lv L, Li B. The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor γt (RORγt) in Th17 cells. J Biol Chem 2014; 289(37): 25546–25555
117. Pal A, Young MA, Donato NJ. Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer. Cancer Res 2014; 74(18): 4955–4966