Th17 cells in central nervous system autoimmunity

Experimental Neurology

Volumn 262, Issue Part A, 2014, Pages 18-27

  Sie, Christopher ^a   Korn, Thomas ^a,b   Mitsdoerffer, Meike ^a,b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b Germany 3 Munich Cluster for Systems Neurology   (Germany)

Author keywords

Experimental autoimmune encephalomyelitis; Multiple sclerosis; Th17 cells

Indexed keywords

ADAPTIVE IMMUNITY; ANTIGEN SPECIFICITY; CYTOKINE RELEASE; DISEASE PREDISPOSITION; EFFECTOR CELL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE MIGRATION; MUCOSAL IMMUNITY; MULTIPLE SCLEROSIS; NONHUMAN; PLASTICITY; REGULATORY MECHANISM; REVIEW; TH17 CELL; ANIMAL; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; IMMUNOLOGY; PATHOLOGY; PHYSIOLOGY;

ANIMALS; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; HUMANS; MULTIPLE SCLEROSIS; TH17 CELLS;

EID: 84908658274     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.03.009     Document Type: Review

References (141)

1. Acosta-Rodriguez E.V., Rivino L., Geginat J., Jarrossay D., Gattorno M., Lanzavecchia A., Sallusto F., Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 2007, 8:639-646.
2. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., Parente E., Filì L., Ferri S., Frosali F., Giudici F., Romagnani P., Parronchi P., Tonelli F., Maggi E., Romagnani S. Phenotypic and functional features of human Th17 cells. J. Exp. Med. 2007, 204:1849-1861.
3. Atarashi K., Nishimura J., Shima T., Umesaki Y., Yamamoto M., Onoue M., Yagita H., Ishii N., Evans R., Honda K., Takeda K. ATP drives lamina propria TH17 cell differentiation. Nature 2008, 455:808-812.
4. Axtell R.C., de Jong B.A., Boniface K., van der Voort L.F., Bhat R., De Sarno P., Naves R., Han M., Zhong F., Castellanos J.G., Mair R., Christakos A., Kolkowitz I., Katz L., Killestein J., Polman C.H., de Waal Malefyt R., Steinman L., Raman C. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat. Med. 2010, 16:406-412.
5. Axtell R.C., Raman C., Steinman L. Interferon-β exacerbates Th17-mediated inflammatory disease. Trends Immunol. 2011, 32:272-277.
6. Bartholomäus I., Kawakami N., Odoardi F., Schläger C., Miljkovic D., Ellwart J.W., Klinkert W.E.F., Flügel-Koch C., Issekutz T.B., Wekerle H., Flügel A. Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 2009, 462:94-98.
7. Becher B., Durell B.G., Noelle R.J. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 2002, 110:493-497.
8. Ben-Nun A., Wekerle H., Cohen I.R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 1981, 11:195-199.
9. Berer K., Krishnamoorthy G. Commensal gut flora and brain autoimmunity: a love or hate affair?. Acta Neuropathol. 2012, 123:639-651.
10. Berer K., Mues M., Koutrolos M., Rasbi Z.Al, Boziki M., Johner C., Wekerle H., Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011, 479:538-541.
11. Bettelli E., Carrier Y., Gao W., Korn T., Strom T.B., Oukka M., Weiner H.L., Kuchroo V.K. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006, 441:235-238.
12. Brown I.J., Tzoulaki I., Candeias V., Elliott P. Salt intakes around the world: implications for public health. Int. J. Epidemiol. 2009, 38:791-813.
13. Brucklacher-Waldert V., Stuerner K., Kolster M., Wolthausen J., Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 2009, 132:3329-3341.
14. Bushnell S.E., Zhao Z., Stebbins C.C., Cadavid D., Buko A.M., Whalley E.T., Davis J.A., Versage E.M., Richert J.R., Axtell R.C., Steinman L., Medori R. Serum IL-17F does not predict poor response to IM IFNβ-1a in relapsing-remitting MS. Neurology 2012, 79:531-537.
15. Carlson T., Kroenke M., Rao P., Lane T.E., Segal B. The Th17-ELR+CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J. Exp. Med. 2008, 205:811-823.
16. Chaudhry A., Rudra D., Treuting P., Samstein R.M., Liang Y., Kas A., Rudensky A.Y. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 2009, 326:986-991.
17. Chaudhry A., Samstein R.M., Treuting P., Liang Y., Pils M.C., Heinrich J.-M., Jack R.S., Wunderlich F.T., Brüning J.C., Müller W., Rudensky A.Y. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 2011, 34:566-578.
18. Chen Y., Langrish C.L., McKenzie B., Joyce-Shaikh B., Stumhofer J.S., McClanahan T., Blumenschein W., Churakovsa T., Low J., Presta L., Hunter C.A., Kastelein R.A., Cua D.J. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J. Clin. Invest. 2006, 116:1317-1326.
19. 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, 12:560-567.
20. Coquet J.M., Chakravarti S., Smyth M.J., Godfrey D.I. Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J. Immunol. 2008, 180:7097-7101.
21. Cosmi L., De Palma R., Santarlasci V., Maggi L., Capone M., Frosali F., Rodolico G., Querci V., Abbate G., Angeli R., Berrino L., Fambrini M., Caproni M., Tonelli F., Lazzeri E., Parronchi P., Liotta F., Maggi E., Romagnani S., Annunziato F. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J. Exp. Med. 2008, 205:1903-1916.
22. Croxford A.L., Mair F., Becher B. IL-23: one cytokine in control of autoimmunity. Eur. J. Immunol. 2012, 42:2263-2273.
23. Cua D.J., Sherlock J., Chen Y., Murphy C.A., Joyce B., Seymour B., Lucian L., To W., Kwan S., Churakova T., Zurawski S., Wiekowski M., Lira S.A., Gorman D., Kastelein R.A., Sedgwick J.D. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003, 421:744-748.
24. Dardalhon V., Korn T., Kuchroo V.K., Anderson A.C. Role of Th1 and Th17 cells in organ-specific autoimmunity. J. Autoimmun. 2008, 31:252-256.
25. Das Sarma J., Ciric B., Marek R., Sadhukhan S., Caruso M.L., Shafagh J., Fitzgerald D.C., Shindler K.S., Rostami A. Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis. J. Neuroinflammation 2009, 6:14.
26. Duhen R., Glatigny S., Arbelaez C.A., Blair T.C., Oukka M., Bettelli E. Cutting edge: the pathogenicity of IFN-γ-producing Th17 cells is independent of T-bet. J. Immunol. 2013, 190:4478-4482.
27. Durelli L., Conti L., Clerico M., Boselli D., Contessa G., Ripellino P., Ferrero B., Eid P., Novelli F. T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta. Ann. Neurol. 2009, 65:499-509.
28. El-behi M., Ciric B., Dai H., Yan Y., Cullimore M., Safavi F., Zhang G.-X., Dittel B.N., 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, 12:568-575.
29. Ely L.K., Fischer S., Garcia K.C. Structural basis of receptor sharing by interleukin 17 cytokines. Nat. Immunol. 2009, 10:1245-1251.
30. Elyaman W., Bradshaw E.M., Uyttenhove C., Dardalhon V., Awasthi A., Imitola J., Bettelli E., Oukka M., Van Snick J., Renauld J.-C., Kuchroo V.K., Khoury S.J. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc. Natl. Acad. Sci. 2009, 106:12885-12890.
31. Engelhardt B., Ransohoff R.M. Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol. 2012, 33:579-589.
32. Fang Y., Yu S., Ellis J.S., Sharav T., Braley-Mullen H. Comparison of sensitivity of Th1, Th2, and Th17 cells to Fas-mediated apoptosis. J. Leukoc. Biol. 2010, 87:1019-1028.
33. Ferber I.A., Brocke S., Taylor-Edwards C., Ridgway W., Dinisco C., Steinman L., Dalton D., Fathman C.G. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 1996, 156:5-7.
34. Filipovic R., Jakovcevski I., Zecevic N. GRO-alpha and CXCR2 in the human fetal brain and multiple sclerosis lesions. Dev. Neurosci. 2003, 25:279-290.
35. Fletcher J.M., Lalor S.J., Sweeney C.M., Tubridy N., Mills K.H.G. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 2010, 162:1-11.
36. Gaboriau-Routhiau V., Rakotobe S., Lécuyer E., Mulder I., Lan A., Bridonneau C., Rochet V., Pisi A., De Paepe M., Brandi G., Eberl G., Snel J., Kelly D., Cerf-Bensussan N. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009, 31:677-689.
37. Gaffen S.L. Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol. 2009, 9:556-567.
38. Ghoreschi K., Laurence A., Yang X.-P., Tato C.M., McGeachy M.J., Konkel J.E., Ramos H.L., Wei L., Davidson T.S., Bouladoux N., Grainger J.R., Chen Q., Kanno Y., Watford W.T., Sun H.-W., Eberl G., Shevach E.M., Belkaid Y., Cua D.J., Chen W., O'Shea J.J. Generation of pathogenic TH17 cells in the absence of TGFbeta signalling. Nature 2010, 467:967-971.
39. Glatigny S., Duhen R., Oukka M., Bettelli E. Cutting edge: loss of α4 integrin expression differentially affects the homing of Th1 and Th17 cells. J. Immunol. 2011, 187:6176-6179.
40. Gold R., Linington C., Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006, 129:1953-1971.
41. Goswami R., Kaplan M.H. A brief history of IL-9. J. Immunol. 2011, 186:3283-3288.
42. Gran B., Zhang G.-X., Yu S., Li J., Chen X.-H., Ventura E.S., Kamoun M., Rostami A. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J. Immunol. 2002, 169:7104-7110.
43. Gu Y., Yang Jianfei, Ouyang X., Liu W., Li H., Yang Jianjun, Bromberg J., Chen S.-H., Mayer L., Unkeless J.C., Xiong H. Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. Eur. J. Immunol. 2008, 38:1807-1813.
44. Haak S., Croxford A.L., Kreymborg K., Heppner F.L., Pouly S., Becher B., Waisman A. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J. Clin. Invest. 2008, 119(1):61-69.
45. Hamilton J.A. Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 2008, 8:533-544.
46. Harrington L.E., Hatton R.D., Mangan P.R., Turner H., Murphy T.L., Murphy K.M., Weaver C.T. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 2005, 6:1123-1132.
47. Hedegaard C.J., Krakauer M., Bendtzen K., Lund H., Sellebjerg F., Nielsen C.H. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 2008, 125:161-169.
48. Henao-Mejia J., Elinav E., Jin C., Hao L., Mehal W.Z., Strowig T., Thaiss C.A., Kau A.L., Eisenbarth S.C., Jurczak M.J., Camporez J.-P., Shulman G.I., Gordon J.I., Hoffman H.M., Flavell R.A. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012, 482:179-185.
49. Hirahara K., Poholek A., Vahedi G., Laurence A., Kanno Y., Milner J.D., O'Shea J.J. Mechanisms underlying helper T-cell plasticity: Implications for immune-mediated disease. J. Allergy Clin. Immunol. 2013, 131:1276-1287.
50. Hirota K., Duarte J.H., Veldhoen M., Hornsby E., Li Y., Cua D.J., Ahlfors H., Wilhelm C., Tolaini M., Menzel U., Garefalaki A., Potocnik A.J., Stockinger B. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol. 2011, 12:255-263.
51. Hsu H.-C., Yang P., Wang J., Wu Q., Myers R., Chen J., Yi J., Guentert T., Tousson A., Stanus A.L., Le T.L., Lorenz R.G., Xu H., Kolls J.K., Carter R.H., Chaplin D.D., Williams R.W., Mountz J.D. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat. Immunol. 2008, 9:166-175.
52. Hu W., Troutman T.D., Edukulla R., Pasare C. Priming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment. Immunity 2011, 35:1010-1022.
53. Huppert J., Closhen D., Croxford A., White R., Kulig P., Pietrowski E., Bechmann I., Becher B., Luhmann H.J., Waisman A., Kuhlmann C.R.W. Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J. 2010, 24:1023-1034.
54. Ishizu T., Osoegawa M., Mei F.-J., Kikuchi H., Tanaka M., Takakura Y., Minohara M., Murai H., Mihara F., Taniwaki T., Kira J. Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 2005, 128:988-1002.
55. Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A., Lafaille J.J., Cua D.J., Littman D.R. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006, 126:1121-1133.
56. Ivanov I.I., Frutos R.deL., Manel N., Yoshinaga K., Rifkin D.B., Sartor R.B., Finlay B.B., Littman D.R. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 2008, 4:337-349.
57. Ivanov I.I., Atarashi K., Manel N., Brodie E.L., Shima T., Karaoz U., Wei D., Goldfarb K.C., Santee C.A., Lynch S.V., Tanoue T., Imaoka A., Itoh K., Takeda K., Umesaki Y., Honda K., Littman D.R. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009, 139:485-498.
58. Jäger A., Dardalhon V., Sobel R.A., Bettelli E., Kuchroo V.K. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J. Immunol. 2009, 183:7169-7177.
59. Jankovic D., Kugler D.G., Sher A. IL-10 production by CD4+ effector T cells: a mechanism for self-regulation. Mucosal Immunol. 2010, 3:239-246.
60. Kang Z., Altuntas C.Z., Gulen M.F., Liu C., Giltiay N., Qin H., Liu L., Qian W., Ransohoff R.M., Bergmann C., Stohlman S., Tuohy V.K., Li X. Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. Immunity 2010, 32:414-425.
61. Kang Z., Wang C., Zepp J., Wu L., Sun K., Zhao J., Chandrasekharan U., DiCorleto P.E., Trapp B.D., Ransohoff R.M., Li X. Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells. Nat. Neurosci. 2013, 16:1401-1408.
62. Kawanokuchi J., Shimizu K., Nitta A., Yamada K., Mizuno T., Takeuchi H., Suzumura A. Production and functions of IL-17 in microglia. J. Neuroimmunol. 2008, 194:54-61.
63. Kebir H., Kreymborg K., Ifergan I., Dodelet-Devillers A., Cayrol R., Bernard M., Giuliani F., Arbour N., Becher B., Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 2007, 13:1173-1175.
64. Kebir H., Ifergan I., Alvarez J.I., Bernard M., Poirier J., Arbour N., Duquette P., Prat A. Preferential recruitment of interferon-γ-expressing TH17 cells in multiple sclerosis. Ann. Neurol. 2009, 66:390-402.
65. Kermode A.G., Thompson A.J., Tofts P., MacManus D.G., Kendall B.E., Kingsley D.P., Moseley I.F., Rudge P., McDonald W.I. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 1990, 113(Pt 5):1477-1489.
66. Kleinewietfeld M., Manzel A., Titze J., Kvakan H., Yosef N., Linker R.A., Muller D.N., Hafler D.A. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 2013, 496:518-522.
67. Kleiter I., Hellwig K., Berthele A., Al E. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch. Neurol. 2012, 69:239-245.
68. Koch-Henriksen N., Sørensen P.S. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010, 9:520-532.
69. Kolls J.K., Lindén A. Interleukin-17 family members and inflammation. Immunity 2004, 21:467-476.
70. Komiyama Y., Nakae S., Matsuki T., Nambu A., Ishigame H., Kakuta S., Sudo K., Iwakura Y. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 2006, 177:566-573.
71. Korn T., Bettelli E., Gao W., Awasthi A., Jager A., Strom T.B., Oukka M., Kuchroo V.K. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 2007, 448:484-487.
72. Korn T., Bettelli E., Oukka M., Kuchroo V.K. IL-17 and Th17 cells. Annu. Rev. Immunol. 2009, 27:485-517.
73. Kreymborg K., Etzensperger R., Dumoutier L., Haak S., Rebollo A., Buch T., Heppner F.L., Renauld J.-C., 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, 179:8098-8104.
74. Kroenke M.A., Carlson T.J., Andjelkovic A.V., Segal B.M. IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J. Exp. Med. 2008, 205:1535-1541.
75. Lampropoulou V., Hoehlig K., Roch T., Neves P., Gómez E.C., Sweenie C.H., Hao Y., Freitas A.A., Steinhoff U., Anderton S.M., Fillatreau S. TLR-activated B cells suppress T cell-mediated autoimmunity. J. Immunol. 2008, 180:4763-4773.
76. Langrish C.L., Chen Y., Blumenschein W.M., Mattson J., Basham B., Sedgwick J.D., McClanahan T., Kastelein R.A., Cua D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 2005, 201:233-240.
77. Lavasani S., Dzhambazov B., Nouri M., Fåk F., Buske S., Molin G., Thorlacius H., Alenfall J., Jeppsson B., Weström B., Unutmaz D. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010, 5:e9009.
78. Lazarevic V., Chen X., Shim J.-H., Hwang E.-S., Jang E., Bolm A.N., Oukka M., Kuchroo V.K., Glimcher L.H. T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR[gamma]t. Nat. Immunol. 2011, 12:96-104.
79. Lee Y.K., Turner H., Maynard C.L., Oliver J.R., Chen D., Elson C.O., Weaver C.T. Late developmental plasticity in the T helper 17 lineage. Immunity 2009, 30:92-107.
80. Lee Y.K., Menezes J.S., Umesaki Y., Mazmanian S.K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. 2011, 108:4615-4622.
81. Lee Y., Awasthi A., Yosef N., Quintana F.J., Xiao S., Peters A., Wu C., Kleinewietfeld M., Kunder S., Hafler D.A., Sobel R.A., Regev A., Kuchroo V.K. Induction and molecular signature of pathogenic TH17 cells. Nat. Immunol. 2012, 13:991-999.
82. Lees J.R., Golumbek P.T., Sim J., Dorsey D., Russell J.H. Regional CNS responses to IFN-gamma determine lesion localization patterns during EAE pathogenesis. J. Exp. Med. 2008, 205:2633-2642.
83. Li M.O., Flavell R.A. Contextual regulation of inflammation: a duet by transforming growth factor-beta and interleukin-10. Immunity 2008, 28:468-476.
84. Liang S.C., Long A.J., Bennett F., Whitters M.J., Karim R., Collins M., Goldman S.J., Dunussi-Joannopoulos K., Williams C.M.M., Wright J.F., Fouser L.A. An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J. Immunol. 2007, 179:7791-7799.
85. Liu S., Song X., Chrunyk B.A., Shanker S., Hoth L.R., Marr E.S., Griffor M.C. Crystal structures of interleukin 17A and its complex with IL-17 receptor A. Nat. Commun. 2013, 4:1888.
86. 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 S.J., Oksenberg J.R., Raine C.S., Heller R., Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 2002, 8:500-508.
87. Magliozzi R., Howell O., Vora A., Serafini B., Nicholas R., Puopolo M., Reynolds R., Aloisi F. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007, 130:1089-1104.
88. Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C., Elson C.O., Hatton R.D., Wahl S.M., Schoeb T.R., Weaver C.T. Transforming growth factor-β induces development of the TH17 lineage. Nature 2006, 441:231-234.
89. Matusevicius D., Kivisäkk P., He B., Kostulas N., Ozenci V., Fredrikson S., Link H. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler. 1999, 5:101-104.
90. McGeachy M.J., Bak-Jensen K.S., Chen Y., Tato C.M., Blumenschein W., McClanahan T., Cua D.J. 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. 2007, 8:1390-1397.
91. McGeachy M.J., Chen Y., Tato C.M., Laurence A., Joyce-Shaikh B., Blumenschein W.M., McClanahan T.K., O'Shea J.J., Cua D.J. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 2009, 10:314-324.
92. McQualter J.L., Darwiche R., Ewing C., Onuki M., Kay T.W., Hamilton J.A., Reid H.H., Bernard C.C.A. Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J. Exp. Med. 2001, 194:873-882.
93. Mehling M., Lindberg R., Raulf F., Kuhle J., Hess C., Kappos L., Brinkmann V. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology 2010, 75:403-410.
94. Minagar A., Alexander J.S. Blood-brain barrier disruption in multiple sclerosis. Mult. Scler. 2003, 9:540-549.
95. Mitsdoerffer M., Lee Y., Jäger A., Kim H.-J., Korn T., Kolls J.K., Cantor H., Bettelli E., Kuchroo V.K. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc. Natl. Acad. Sci. 2010, 107:14292-14297.
96. Montes M., Zhang X., Berthelot L., Laplaud D.-A., Brouard S., Jin J., Rogan S., Armao D., Jewells V., Soulillou J.-P., Markovic-Plese S. Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells. Clin. Immunol. 2009, 130:133-144.
97. Mosmann T.R., Cherwinski H., Bond M.W., Giedlin M.A., Coffman R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 1986, 136:2348-2357.
98. Murphy E., Shibuya K., Hosken N., Openshaw P., Maino V., Davis K., Murphy K., O'Garra A. Reversibility of T helper 1 and 2 populations is lost after long-term stimulation. J. Exp. Med. 1996, 183:901-913.
99. Nowak E.C., Weaver C.T., Turner H., Begum-Haque S., Becher B., Schreiner B., Coyle A.J., Kasper L.H., Noelle R.J. IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med. 2009, 206:1653-1660.
100. Nurieva R., Yang X.O., Martinez G., Zhang Y., Panopoulos A.D., Ma L., Schluns K., Tian Q., Watowich S.S., Jetten A.M., Dong C. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007, 448:480-483.
101. Ochoa-Repáraz J., Mielcarz D.W., Wang Y., Begum-Haque S., Dasgupta S., Kasper D.L., Kasper L.H. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010, 3:487-495.
102. Odoardi F., Sie C., Streyl K., Ulaganathan V.K., Schläger C., Lodygin D., Heckelsmiller K., Nietfeld W., Ellwart J., Klinkert W.E.F., Lottaz C., Nosov M., Brinkmann V., Spang R., Lehrach H., Vingron M., Wekerle H., Flügel-Koch C., Flügel A. T cells become licensed in the lung to enter the central nervous system. Nature 2012, 488:675-679.
103. Oppmann B., Lesley R., Blom B., Timans J.C., 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.-J., Abrams J.S., Moore K.W., Rennick D., de Waal-Malefyt R., Hannum C., Bazan J.F., Kastelein R.A. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000, 13:715-725.
104. Ouyang W., Kolls J.K., Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 2008, 28:454-467.
105. Paintlia M.K., Paintlia A.S., Singh A.K., Singh I. Synergistic activity of interleukin-17 and tumor necrosis factor-α enhances oxidative stress-mediated oligodendrocyte apoptosis. J. Neurochem. 2011, 116:508-521.
106. Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T., Zurawski S., Hannum C., Gorman D., Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 2002, 168:5699-5708.
107. Peng H., Guerau-de-Arellano M., Mehta V.B., Yang Y., Huss D.J., Papenfuss T.L., Lovett-Racke A.E., Racke M.K. Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor κB (NF-κB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling. J. Biol. Chem. 2012, 287:28017-28026.
108. Perdew G.H., Babbs C.F. Production of ah receptor ligands in rat fecal suspensions containing tryptophan or indole-3-carbinol. Nutr. Cancer 1991, 16:209-218.
109. Peters A., Pitcher L.A., Sullivan J.M., Mitsdoerffer M., Acton S.E., Franz B., Wucherpfennig K., Turley S., Carroll M.C., Sobel R.A., Bettelli E., Kuchroo V.K. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity 2011, 35:986-996.
110. Quintana F.J., Basso A.S., Iglesias A.H., Korn T., Farez M.F., Bettelli E., Caccamo M., Oukka M., Weiner H.L. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 2008, 453:65-71.
111. Ramgolam V.S., Sha Y., Jin J., Zhang X., Markovic-Plese S. IFN-beta inhibits human Th17 cell differentiation. J. Immunol. 2009, 183:5418-5427.
112. Rangachari M., Kuchroo V.K. Using EAE to better understand principles of immune function and autoimmune pathology. J. Autoimmun. 2013, 45:31-39.
113. 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, 10:514-523.
114. Rothhammer V., Heink S., Petermann F., Srivastava R., Claussen M.C., Hemmer B., Korn T. Th17 lymphocytes traffic to the central nervous system independently of α4 integrin expression during EAE. J. Exp. Med. 2011, 208:2465-2476.
115. Sawcer S., Hellenthal G., Pirinen M., Spencer C.C.A., Patsopoulos N.A., et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011, 476:214-219.
116. Schluesener H.J., Wekerle H. Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: in vitro selection from unprimed rat T lymphocyte populations. J. Immunol. 1985, 135:3128-3133.
117. Segal B.M., Dwyer B.K., Shevach E.M. An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. J. Exp. Med. 1998, 187:537-546.
118. Segal B.M., Constantinescu C.S., Raychaudhuri A., Kim L., Fidelus-Gort R., Kasper L.H., Investigators U.M.S. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol. 2008, 7:796-804.
119. Serafini B., Rosicarelli B., Magliozzi R., Stigliano E., Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 2004, 14:164-174.
120. Siffrin V., Radbruch H., Glumm R., Niesner R., Paterka M., Herz J., Leuenberger T., Lehmann S.M., Luenstedt S., Rinnenthal J.L., Laube G., Luche H., Lehnardt S., Fehling H.-J., Griesbeck O., Zipp F. In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 2010, 33:424-436.
121. Sonderegger I., Iezzi G., Maier R., Schmitz N., Kurrer M., Kopf M. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J. Exp. Med. 2008, 205:2281-2294.
122. 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, 38:1833-1838.
123. Stromnes I.M., Cerretti L.M., Liggitt D., Harris R.A., Goverman J.M. Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells. Nat. Med. 2008, 14:337-342.
124. Sweeney C.M., Lonergan R., Basdeo S.A., Kinsella K., Dungan L.S., Higgins S.C., Kelly P.J., Costelloe L., Tubridy N., Mills K.H.G., Fletcher J.M. IL-27 mediates the response to IFN-β therapy in multiple sclerosis patients by inhibiting Th17 cells. Brain Behav. Immun. 2011, 25:1170-1181.
125. Tigno-Aranjuez J.T., Jaini R., Tuohy V.K., Lehmann P.V., Tary-Lehmann M. Encephalitogenicity of complete Freund's adjuvant relative to CpG is linked to induction of Th17 cells. J. Immunol. 2009, 183:5654-5661.
126. Traugott U., Lebon P. Interferon-gamma and Ia antigen are present on astrocytes in active chronic multiple sclerosis lesions. J. Neurol. Sci. 1988, 84:257-264.
127. Traugott U., Lebon P. Multiple sclerosis: involvement of interferons in lesion pathogenesis. Ann. Neurol. 1988, 24:243-251.
128. Tzartos J.S., Friese M.A., Craner M.J., Palace J., Newcombe J., Esiri M.M., Fugger L. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol. 2008, 172:146-155.
129. Uyttenhove C., Van Snick J. Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis. Eur. J. Immunol. 2006, 36:2868-2874.
130. Vaknin-Dembinsky A., Balashov K., Weiner H.L. IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J. Immunol. 2006, 176:7768-7774.
131. Varrin-Doyer M., Spencer C.M., Schulze-Topphoff U., Nelson P.A., Stroud R.M., Cree B.A.C., Zamvil S.S. Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann. Neurol. 2012, 72:53-64.
132. Veldhoen M., Hocking R.J., Atkins C.J., Locksley R.M., Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006, 24:179-189.
133. Veldhoen M., Hirota K., Westendorf A.M., Buer J., Dumoutier L., Renauld J.-C., Stockinger B. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008, 453:106-109.
134. Wang H.H., Dai Y.Q., Qiu W., Lu Z.Q., Peng F.H., Wang Y.G., Bao J., Li Y., Hu X.Q. Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse. J. Clin. Neurosci. 2011, 18:1313-1317.
135. Wikoff W.R., Anfora A.T., Liu J., Schultz P.G., Lesley S.A., Peters E.C., Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. 2009, 106:3698-3703.
136. Willenborg D.O., Fordham S., Bernard C.C., Cowden W.B., Ramshaw I.A. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 1996, 157:3223-3227.
137. Wu C., Yosef N., Thalhamer T., Zhu C., Xiao S., Kishi Y., Regev A., Kuchroo V.K. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 2013, 496:513-517.
138. Zamvil S.S., Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 1990, 8:579-621.
139. Zhang G.-X., Gran B., Yu S., Li J., Siglienti I., Chen X., Kamoun M., Rostami A. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-β2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J. Immunol. 2003, 170:2153-2160.
140. Zhang Y., Xu G., Zhang L., Roberts A.I., Shi Y. Th17 cells undergo Fas-mediated activation-induced cell death independent of IFN-gamma. J. Immunol. 2008, 181:190-196.
141. Zhou L., Ivanov I.I., Spolski R., Min R., Shenderov K., Egawa T., Levy D.E., Leonard W.J., Littman D.R. IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 2007, 8:967-974.