The pathogenicity of Th17 cells in autoimmune diseases

1.

Gaffen SL, Jain R, Garg AV, Cua DJ (2014) The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol 14(9):585–600. https://doi.org/10.1038/nri3707 CrossRefPubMedPubMedCentral

2.

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. https://doi.org/10.1038/ni1254 CrossRefPubMed

3.

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. https://doi.org/10.1038/ni1261 CrossRefPubMedPubMedCentral

4.

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. https://doi.org/10.1038/nature04753 CrossRefPubMed

5.

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. https://doi.org/10.1038/nature04754 CrossRefPubMed

6.

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. https://doi.org/10.1016/j.immuni.2006.01.001 CrossRefPubMed

7.

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. https://doi.org/10.1038/ni1488 CrossRefPubMed

8.

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. https://doi.org/10.1016/j.cell.2006.07.035 CrossRefPubMed

9.

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. https://doi.org/10.1016/j.immuni.2007.11.016 CrossRefPubMed

10.

Zhong Z, Wen Z, Darnell JE Jr (1994) Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264(5155):95–98CrossRefPubMed

11.

Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S (1998) Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol 161(9):4652–4660PubMed

12.

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. https://doi.org/10.1074/jbc.C600321200 CrossRefPubMed

13.

Littman DR, Rudensky AY (2010) Th17 and regulatory T cells in mediating and restraining inflammation. Cell 140(6):845–858. https://doi.org/10.1016/j.cell.2010.02.021 CrossRefPubMed

14.

Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A (1998) IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28(7):2178–2187. https://doi.org/10.1002/(SICI)1521-4141(199807)28:07<2178::AID-IMMU2178>3.0.CO;2-D CrossRefPubMed

15.

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. https://doi.org/10.1038/nature09447 CrossRefPubMedPubMedCentral

16.

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. https://doi.org/10.1016/j.immuni.2007.02.009 CrossRefPubMed

17.

Kim HS, Jang SW, Lee W, Kim K, Sohn H, Hwang SS, Lee GR (2017) PTEN drives Th17 cell differentiation by preventing IL-2 production. J Exp Med 214(11):3381–3398. https://doi.org/10.1084/jem.20170523 CrossRefPubMedPubMedCentral

18.

Quintana FJ, Jin H, Burns EJ, Nadeau M, Yeste A, Kumar D, Rangachari M, Zhu C, Xiao S, Seavitt J, Georgopoulos K, Kuchroo VK (2012) Aiolos promotes TH17 differentiation by directly silencing Il2 expression. Nat Immunol 13(8):770–777. https://doi.org/10.1038/ni.2363 CrossRefPubMedPubMedCentral

19.

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. https://doi.org/10.1016/j.cell.2009.09.033 CrossRefPubMedPubMedCentral

20.

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. https://doi.org/10.1084/jem.20061308 CrossRefPubMedPubMedCentral

21.

Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM, Stockinger B (2013) Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14(4):372–379. https://doi.org/10.1038/ni.2552 CrossRefPubMedPubMedCentral

22.

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. https://doi.org/10.1038/nature01355 CrossRefPubMed

23.

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. https://doi.org/10.1084/jem.20041257 CrossRefPubMedPubMedCentral

24.

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. https://doi.org/10.1016/j.immuni.2009.02.007 CrossRefPubMedPubMedCentral

25.

Schiffenbauer J, Streit WJ, Butfiloski E, LaBow M, Edwards C 3rd, Moldawer LL (2000) The induction of EAE is only partially dependent on TNF receptor signaling but requires the IL-1 type I receptor. Clin Immunol 95(2):117–123. https://doi.org/10.1006/clim.2000.4851 CrossRefPubMed

26.

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. https://doi.org/10.1084/jem.20060285 CrossRefPubMedPubMedCentral

27.

Matsuki T, Nakae S, Sudo K, Horai R, Iwakura Y (2006) Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis. Int Immunol 18(2):399–407. https://doi.org/10.1093/intimm/dxh379 CrossRefPubMed

28.

McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O'Shea JJ, Cua DJ (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 10(3):314–324. https://doi.org/10.1038/ni.1698 CrossRefPubMedPubMedCentral

29.

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. https://doi.org/10.1038/ni1539 CrossRefPubMed

30.

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 (2012) Induction and molecular signature of pathogenic TH17 cells. Nat Immunol 13(10):991–999. https://doi.org/10.1038/ni.2416 CrossRefPubMedPubMedCentral

31.

Gaublomme JT, Yosef N, Lee Y, Gertner RS, Yang LV, Wu C, Pandolfi PP, Mak T, Satija R, Shalek AK, Kuchroo VK, Park H, Regev A (2015) Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell 163(6):1400–1412. https://doi.org/10.1016/j.cell.2015.11.009 CrossRefPubMedPubMedCentral

32.

Wang C, Yosef N, Gaublomme J, Wu C, Lee Y, Clish CB, Kaminski J, Xiao S, Meyer Zu Horste G, Pawlak M, Kishi Y, Joller N, Karwacz K, Zhu C, Ordovas-Montanes M, Madi A, Wortman I, Miyazaki T, Sobel RA, Park H, Regev A, Kuchroo VK (2015) CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity. Cell 163(6):1413–1427. https://doi.org/10.1016/j.cell.2015.10.068 CrossRefPubMedPubMedCentral

33.

Carr TM, Wheaton JD, Houtz GM, Ciofani M (2017) JunB promotes Th17 cell identity and restrains alternative CD4(+) T-cell programs during inflammation. Nat Commun 8(1):301. https://doi.org/10.1038/s41467-017-00380-3 CrossRefPubMedPubMedCentral

34.

Hasan Z, Koizumi SI, Sasaki D, Yamada H, Arakaki N, Fujihara Y, Okitsu S, Shirahata H, Ishikawa H (2017) JunB is essential for IL-23-dependent pathogenicity of Th17 cells. Nat Commun 8:15628. https://doi.org/10.1038/ncomms15628 CrossRefPubMedPubMedCentral

35.

Basu R, Whitley SK, Bhaumik S, Zindl CL, Schoeb TR, Benveniste EN, Pear WS, Hatton RD, Weaver CT (2015) IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell-iTreg cell balance. Nat Immunol 16(3):286–295. https://doi.org/10.1038/ni.3099 CrossRefPubMedPubMedCentral

36.

Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B (2011) Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12(3):255–263. https://doi.org/10.1038/ni.1993 CrossRefPubMedPubMedCentral

37.

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):715–725CrossRefPubMed

38.

Ichiyama K, Gonzalez-Martin A, Kim BS, Jin HY, Jin W, Xu W, Sabouri-Ghomi M, Xu S, Zheng P, Xiao C, Dong C (2016) The microRNA-183-96-182 cluster promotes T helper 17 cell pathogenicity by negatively regulating transcription factor Foxo1 expression. Immunity 44(6):1284–1298. https://doi.org/10.1016/j.immuni.2016.05.015 CrossRefPubMedPubMedCentral

39.

Kishi Y, Kondo T, Xiao S, Yosef N, Gaublomme J, Wu C, Wang C, Chihara N, Regev A, Joller N, Kuchroo VK (2016) Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. J Exp Med 213(11):2489–2501. https://doi.org/10.1084/jem.20151118 CrossRefPubMedPubMedCentral

40.

Meyer Zu Horste G, Wu C, Wang C, Cong L, Pawlak M, Lee Y, Elyaman W, Xiao S, Regev A, Kuchroo VK (2016) RBPJ controls development of pathogenic Th17 cells by regulating IL-23 receptor expression. Cell Rep 16(2):392–404. https://doi.org/10.1016/j.celrep.2016.05.088 CrossRefPubMedPubMedCentral

41.

El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A (2011) The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 12(6):568–575. https://doi.org/10.1038/ni.2031 CrossRefPubMedPubMedCentral

42.

Jain R, Chen Y, Kanno Y, Joyce-Shaikh B, Vahedi G, Hirahara K, Blumenschein WM, Sukumar S, Haines CJ, Sadekova S, McClanahan TK, McGeachy MJ, O'Shea JJ, Cua DJ (2016) Interleukin-23-induced transcription factor Blimp-1 promotes pathogenicity of T helper 17 cells. Immunity 44(1):131–142. https://doi.org/10.1016/j.immuni.2015.11.009 CrossRefPubMed

43.

Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65–71. https://doi.org/10.1038/nature06880 CrossRefPubMed

44.

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. https://doi.org/10.1038/nature06881 CrossRefPubMed

45.

Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F (2011) Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146(5):772–784. https://doi.org/10.1016/j.cell.2011.07.033 CrossRefPubMedPubMedCentral

46.

Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208(7):1367–1376. https://doi.org/10.1084/jem.20110278 CrossRefPubMedPubMedCentral

47.

Karmaus PWF, Chen X, Lim SA, Herrada AA, Nguyen TM, Xu B, Dhungana Y, Rankin S, Chen W, Rosencrance C, Yang K, Fan Y, Cheng Y, Easton J, Neale G, Vogel P, Chi H (2018) Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity. Nature. https://doi.org/10.1038/s41586-018-0806-7 CrossRefPubMedPubMedCentral

48.

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. https://doi.org/10.1038/nature11984 CrossRefPubMedPubMedCentral

49.

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. https://doi.org/10.1038/nature11868 CrossRefPubMedPubMedCentral

50.

McQualter JL, Darwiche R, Ewing C, Onuki M, Kay TW, Hamilton JA, Reid HH, Bernard CCA (2001) Granulocyte macrophage colony-stimulating factor. J Exp Med 194(7):873–882. https://doi.org/10.1084/jem.194.7.873 CrossRefPubMedPubMedCentral

51.

Sonderegger I, Iezzi G, Maier R, Schmitz N, Kurrer M, Kopf M (2008) GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med 205(10):2281–2294. https://doi.org/10.1084/jem.20071119 CrossRefPubMedPubMedCentral

52.

Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, Suter T, Becher B (2011) RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 12(6):560–567. https://doi.org/10.1038/ni.2027 CrossRefPubMed

53.

Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD (2007) Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J Immunol 178(8):5245–5252. https://doi.org/10.4049/jimmunol.178.8.5245 CrossRefPubMed

54.

Croxford AL, Lanzinger M, Hartmann FJ, Schreiner B, Mair F, Pelczar P, Clausen BE, Jung S, Greter M, Becher B (2015) The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity. Immunity 43(3):502–514. https://doi.org/10.1016/j.immuni.2015.08.010 CrossRefPubMed

55.

Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN (2006) GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 178(1):39–48. https://doi.org/10.4049/jimmunol.178.1.39 CrossRef

56.

Li J, Gran B, Zhang G-X, Ventura ES, Siglienti I, Rostami A, Kamoun M (2003) Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci 215(1–2):95–103. https://doi.org/10.1016/s0022-510x(03)00203-x CrossRefPubMed

57.

Martinez-Llordella M, Esensten JH, Bailey-Bucktrout SL, Lipsky RH, Marini A, Chen J, Mughal M, Mattson MP, Taub DD, Bluestone JA (2013) CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response. J Exp Med 210(8):1603–1619. https://doi.org/10.1084/jem.20122387 CrossRefPubMedPubMedCentral

58.

Lin CC, Bradstreet TR, Schwarzkopf EA, Jarjour NN, Chou C, Archambault AS, Sim J, Zinselmeyer BH, Carrero JA, Wu GF, Taneja R, Artyomov MN, Russell JH, Edelson BT (2016) IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation. J Exp Med 213(2):251–271. https://doi.org/10.1084/jem.20150568 CrossRefPubMedPubMedCentral

59.

Yasuda K, Kitagawa Y, Kawakami R, Isaka Y, Watanabe H, Kondoh G, Kohwi-Shigematsu T, Sakaguchi S, Hirota K (2019) Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation. Nat Commun 10(1):549. https://doi.org/10.1038/s41467-019-08404-w CrossRefPubMedPubMedCentral

60.

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. https://doi.org/10.1038/ni1496 CrossRefPubMed

61.

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 MR (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957. https://doi.org/10.1038/ni1497 CrossRefPubMed

62.

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. https://doi.org/10.1038/ni.1610 CrossRefPubMedPubMedCentral

63.

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. https://doi.org/10.1038/ni.1613 CrossRefPubMed

64.

Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56(9):2936–2946. https://doi.org/10.1002/art.22866 CrossRefPubMedPubMedCentral

65.

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. https://doi.org/10.1038/nature06096 CrossRefPubMed

66.

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. https://doi.org/10.1038/nature06764 CrossRefPubMedPubMedCentral

67.

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. https://doi.org/10.1038/nm0502-500 CrossRefPubMed

68.

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. https://doi.org/10.1038/nature05970 CrossRefPubMedPubMedCentral

69.

Vaknin-Dembinsky A, Balashov K, Weiner HL (2006) 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 176(12):7768–7774. https://doi.org/10.4049/jimmunol.176.12.7768 CrossRefPubMed

70.

Wen SR, Liu GJ, Feng RN, Gong FC, Zhong H, Duan SR, Bi S (2012) Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 244(1–2):94–96. https://doi.org/10.1016/j.jneuroim.2011.12.004 CrossRefPubMed

71.

Carrieri PB, Provitera V, De Rosa T, Tartaglia G, Gorga F, Perrella O (1998) Profile of cerebrospinal fluid and serum cytokines in patients with relapsing remitting multiple sclerosis: a correlation with clinical activity. Immunopharmacol Immunotoxicol:373–382CrossRefPubMed

72.

Rasouli J, Ciric B, Imitola J, Gonnella P, Hwang D, Mahajan K, Mari ER, Safavi F, Leist TP, Zhang GX, Rostami A (2015) Expression of GM-CSF in T cells is increased in multiple sclerosis and suppressed by IFN-beta therapy. J Immunol 194(11):5085–5093. https://doi.org/10.4049/jimmunol.1403243 CrossRefPubMed

73.

Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388(10055):2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8 CrossRefPubMed

74.

Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30(11):1205–1213CrossRefPubMed

75.

Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH (2002) Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. Semin Arthritis Rheum 31(6):355–360CrossRefPubMed

76.

Lundy SK, Sarkar S, Tesmer LA, Fox DA (2007) Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther 9(1):202. https://doi.org/10.1186/ar2107 CrossRefPubMedPubMedCentral

77.

Firestein GS, Zvaifler NJ (1987) Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. II Low levels of synovial fluid and synovial tissue interferon suggest that gamma-interferon is not the primary macrophage activating factor. Arthritis Rheum 30(8):864–871CrossRefPubMed

78.

Firestein GS, Zvaifler NJ (1990) How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum 33(6):768–773CrossRefPubMed

79.

Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283(5748):666–668CrossRefPubMed

80.

Matsumoto I, Staub A, Benoist C, Mathis D (1999) Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286(5445):1732–1735CrossRefPubMed

81.

Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Mimori T (2009) Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. Arthritis Rheum 60(8):2294–2303. https://doi.org/10.1002/art.24687 CrossRefPubMed

82.

Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S (2007) T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med 204(1):41–47. https://doi.org/10.1084/jem.20062259 CrossRefPubMedPubMedCentral

83.

Iwanami K, Matsumoto I, Tanaka-Watanabe Y, Inoue A, Mihara M, Ohsugi Y, Mamura M, Goto D, Ito S, Tsutsumi A, Kishimoto T, Sumida T (2008) Crucial role of the interleukin-6/interleukin-17 cytokine axis in the induction of arthritis by glucose-6-phosphate isomerase. Arthritis Rheum 58(3):754–763. https://doi.org/10.1002/art.23222 CrossRefPubMed

84.

Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, Sakihama T, Matsutani T, Negishi I, Nakatsuru S, Sakaguchi S (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426(6965):454–460. https://doi.org/10.1038/nature02119 CrossRefPubMed

85.

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. https://doi.org/10.1172/JCI21795 CrossRefPubMedPubMedCentral

86.

Tanaka S, Maeda S, Hashimoto M, Fujimori C, Ito Y, Teradaira S, Hirota K, Yoshitomi H, Katakai T, Shimizu A, Nomura T, Sakaguchi N, Sakaguchi S (2010) Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J Immunol 185(4):2295–2305. https://doi.org/10.4049/jimmunol.1000848 CrossRefPubMed

87.

Yoshitomi H, Sakaguchi N, Kobayashi K, Brown GD, Tagami T, Sakihama T, Hirota K, Tanaka S, Nomura T, Miki I, Gordon S, Akira S, Nakamura T, Sakaguchi S (2005) A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 201(6):949–960. https://doi.org/10.1084/jem.20041758 CrossRefPubMedPubMedCentral

88.

Hashimoto M, Hirota K, Yoshitomi H, Maeda S, Teradaira S, Akizuki S, Prieto-Martin P, Nomura T, Sakaguchi N, Kohl J, Heyman B, Takahashi M, Fujita T, Mimori T, Sakaguchi S (2010) Complement drives Th17 cell differentiation and triggers autoimmune arthritis. J Exp Med 207(6):1135–1143. https://doi.org/10.1084/jem.20092301 CrossRefPubMedPubMedCentral

89.

Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S (2014) Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease. Science 346(6207):363–368. https://doi.org/10.1126/science.1259077 CrossRefPubMedPubMedCentral

90.

Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, Yamaguchi T, Nomura T, Ito H, Nakamura T, Sakaguchi N, Sakaguchi S (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204(12):2803–2812. https://doi.org/10.1084/jem.20071397 CrossRefPubMedPubMedCentral

91.

Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K (2010) A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet 42(6):515–519. https://doi.org/10.1038/ng.583 CrossRefPubMed

92.

Gasson JC (1991) Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood 77(6):1131–1145CrossRefPubMed

93.

Alvaro-Gracia JM, Zvaifler NJ, Brown CB, Kaushansky K, Firestein GS (1991) Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. J Immunol 146(10):3365–3371PubMed

94.

Wright HL, Bucknall RC, Moots RJ, Edwards SW (2012) Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy. Rheumatology (Oxford) 51(3):451–459. https://doi.org/10.1093/rheumatology/ker338 CrossRef

95.

Hirota K, Hashimoto M, Ito Y, Matsuura M, Ito H, Tanaka M, Watanabe H, Kondoh G, Tanaka A, Yasuda K, Kopf M, Potocnik AJ, Stockinger B, Sakaguchi N, Sakaguchi S (2018) Autoimmune Th17 cells induced synovial stromal and innate lymphoid cell secretion of the cytokine GM-CSF to initiate and augment autoimmune arthritis. Immunity 48(6):1220–1232 e1225. https://doi.org/10.1016/j.immuni.2018.04.009 CrossRefPubMedPubMedCentral

96.

Terao C, Raychaudhuri S, Gregersen PK (2016) Recent advances in defining the genetic basis of rheumatoid arthritis. Annu Rev Genomics Hum Genet 17:273–301. https://doi.org/10.1146/annurev-genom-090314-045919 CrossRefPubMedPubMedCentral

97.

Kim K, Bang SY, Lee HS, Bae SC (2017) Update on the genetic architecture of rheumatoid arthritis. Nat Rev Rheumatol 13(1):13–24. https://doi.org/10.1038/nrrheum.2016.176 CrossRefPubMed

98.

Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieude P, Mariette X, Bridges SL Jr, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapaa-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M, consortium R, consortium G, Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K, Plenge RM (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506(7488):376–381. https://doi.org/10.1038/nature12873 CrossRefPubMed

99.

Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, Li Y, Kurreeman FA, Zhernakova A, Hinks A, Guiducci C, Chen R, Alfredsson L, Amos CI, Ardlie KG, Consortium B, Barton A, Bowes J, Brouwer E, Burtt NP, Catanese JJ, Coblyn J, Coenen MJ, Costenbader KH, Criswell LA, Crusius JB, Cui J, de Bakker PI, De Jager PL, Ding B, Emery P, Flynn E, Harrison P, Hocking LJ, Huizinga TW, Kastner DL, Ke X, Lee AT, Liu X, Martin P, Morgan AW, Padyukov L, Posthumus MD, Radstake TR, Reid DM, Seielstad M, Seldin MF, Shadick NA, Steer S, Tak PP, Thomson W, van der Helm-van Mil AH, van der Horst-Bruinsma IE, van der Schoot CE, van Riel PL, Weinblatt ME, Wilson AG, Wolbink GJ, Wordsworth BP, Consortium Y, Wijmenga C, Karlson EW, Toes RE, de Vries N, Begovich AB, Worthington J, Siminovitch KA, Gregersen PK, Klareskog L, Plenge RM (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42(6):508–514. https://doi.org/10.1038/ng.582 CrossRefPubMedPubMedCentral

100.

Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C, Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D, Biologics in Rheumatoid Arthritis G, Genomics Study S, Wellcome Trust Case Control C, Concannon P, Onengut-Gumuscu S, Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Arlsetig L, Martin J, Rantapaa-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L, Gregersen PK, Worthington J (2012) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet 44(12):1336–1340. https://doi.org/10.1038/ng.2462 CrossRefPubMedPubMedCentral

101.

Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, Miossec P (1999) Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42(5):963–970. https://doi.org/10.1002/1529-0131(199905)42:5<963::AID-ANR15>3.0.CO;2-E CrossRefPubMed

102.

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. https://doi.org/10.1172/JCI5703 CrossRefPubMedPubMedCentral

103.

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):2832–2838CrossRefPubMed

104.

Shahrara S, Huang Q, Mandelin AM 2nd, Pope RM (2008) TH-17 cells in rheumatoid arthritis. Arthritis Res Ther 10(4):R93. https://doi.org/10.1186/ar2477 CrossRefPubMedPubMedCentral

105.

Kirkham BW, Lassere MN, Edmonds JP, Juhasz KM, Bird PA, Lee CS, Shnier R, Portek IJ (2006) Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum 54(4):1122–1131. https://doi.org/10.1002/art.21749 CrossRefPubMed

106.

Leipe J, Grunke M, Dechant C, Reindl C, Kerzendorf U, Schulze-Koops H, Skapenko A (2010) Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 62(10):2876–2885. https://doi.org/10.1002/art.27622 CrossRefPubMed

107.

Penatti A, Facciotti F, De Matteis R, Larghi P, Paroni M, Murgo A, De Lucia O, Pagani M, Pierannunzii L, Truzzi M, Ioan-Facsinay A, Abrignani S, Geginat J, Meroni PL (2017) Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 19(1):103. https://doi.org/10.1186/s13075-017-1305-1 CrossRefPubMedPubMedCentral

108.

van Hamburg JP, Asmawidjaja PS, Davelaar N, Mus AM, Colin EM, Hazes JM, Dolhain RJ, Lubberts E (2011) 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 63(1):73–83. https://doi.org/10.1002/art.30093 CrossRefPubMed

109.

Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P (2008) Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 58(8):2307–2317. https://doi.org/10.1002/art.23655 CrossRefPubMed

110.

Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi JI, Kaibara N, Hori A, Iwamoto Y, Yoshikai Y (2008) Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis 67(9):1299–1304. https://doi.org/10.1136/ard.2007.080341 CrossRefPubMed

111.

Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, Melendez AJ, McInnes IB (2010) Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184(7):3336–3340. https://doi.org/10.4049/jimmunol.0903566 CrossRefPubMed

112.

Kan J, Mishima S, Kashiwakura J, Sasaki-Sakamoto T, Seki M, Saito S, Ra C, Tokuhashi Y, Okayama Y (2016) Interleukin-17A expression in human synovial mast cells in rheumatoid arthritis and osteoarthritis. Allergol Int 65(Suppl):S11–S16. https://doi.org/10.1016/j.alit.2016.04.007 CrossRefPubMed

113.

Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, Evans JG, Cimaz R, Bajaj-Elliott M, Wedderburn LR (2010) Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A 107(33):14751–14756. https://doi.org/10.1073/pnas.1003852107 CrossRefPubMedPubMedCentral

114.

Basdeo SA, Cluxton D, Sulaimani J, Moran B, Canavan M, Orr C, Veale DJ, Fearon U, Fletcher JM (2017) Ex-Th17 (nonclassical Th1) cells are functionally distinct from classical Th1 and Th17 cells and are not constrained by regulatory T cells. J Immunol 198(6):2249–2259. https://doi.org/10.4049/jimmunol.1600737 CrossRefPubMed

115.

Cosmi L, Cimaz R, Maggi L, Santarlasci V, Capone M, Borriello F, Frosali F, Querci V, Simonini G, Barra G, Piccinni MP, Liotta F, De Palma R, Maggi E, Romagnani S, Annunziato F (2011) Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis. Arthritis Rheum 63(8):2504–2515. https://doi.org/10.1002/art.30332 CrossRefPubMed

116.

Yamada H, Haraguchi A, Sakuraba K, Okazaki K, Fukushi JI, Mizu-Uchi H, Akasaki Y, Esaki Y, Kamura S, Fujimura K, Kondo M, Miyahara H, Nakashima Y, Yoshikai Y (2017) Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis. RMD Open 3(1):e000487. https://doi.org/10.1136/rmdopen-2017-000487 CrossRefPubMedPubMedCentral

117.

Piper C, Pesenacker AM, Bending D, Thirugnanabalan B, Varsani H, Wedderburn LR, Nistala K (2014) T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity. Arthritis Rheum 66(7):1955–1960. https://doi.org/10.1002/art.38647 CrossRef

118.

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. https://doi.org/10.1136/annrheumdis-2012-201601 CrossRefPubMed

119.

Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY, Banerjee S (2014) A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheum 66(7):1693–1704. https://doi.org/10.1002/art.38617 CrossRef

120.

Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Ligozio G, Mpofu S (2014) One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study. J Rheumatol 41(3):414–421. https://doi.org/10.3899/jrheum.130637 CrossRefPubMed

121.

Genovese MC, Braun DK, Erickson JS, Berclaz PY, Banerjee S, Heffernan MP, Carlier H (2016) Safety and efficacy of open-label subcutaneous Ixekizumab treatment for 48 weeks in a phase II study in biologic-naive and TNF-IR patients with rheumatoid arthritis. J Rheumatol 43(2):289–297. https://doi.org/10.3899/jrheum.140831 CrossRefPubMed

122.

Blanco FJ, Moricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H (2017) Secukinumab in active rheumatoid arthritis: a phase III randomized, double-blind, active comparator- and placebo-controlled study. Arthritis Rheum 69(6):1144–1153. https://doi.org/10.1002/art.40070 CrossRef

123.

Dokoupilova E, Aelion J, Takeuchi T, Malavolta N, Sfikakis PP, Wang Y, Rohrer S, Richards HB (2018) Secukinumab after anti-tumour necrosis factor-alpha therapy: a phase III study in active rheumatoid arthritis. Scand J Rheumatol 47(4):276–281. https://doi.org/10.1080/03009742.2017.1390605 CrossRefPubMed

124.

Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M (2005) Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther 7(4):R784–R795. https://doi.org/10.1186/ar1733 CrossRefPubMedPubMedCentral

125.

Kokkonen H, Soderstrom I, Rocklov J, Hallmans G, Lejon K, Rantapaa Dahlqvist S (2010) Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum 62(2):383–391. https://doi.org/10.1002/art.27186 CrossRefPubMed

126.

Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW, Berenfus VY, Vladeva S, Rech J, Rubbert-Roth A, Korkosz M, Rekalov D, Zupanets IA, Ejbjerg BJ, Geiseler J, Fresenius J, Korolkiewicz RP, Schottelius AJ, Burkhardt H (2015) MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis 74(6):1058–1064. https://doi.org/10.1136/annrheumdis-2013-204816 CrossRefPubMed

127.

Burmester GR, Weinblatt ME, IB MI, Porter D, Barbarash O, Vatutin M, Szombati I, Esfandiari E, Sleeman MA, Kane CD, Cavet G, Wang B, Godwood A, Magrini F, Group ES (2013) Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis 72(9):1445–1452. https://doi.org/10.1136/annrheumdis-2012-202450 CrossRefPubMed

128.

Burmester GR, McInnes IB, Kremer J, Miranda P, Korkosz M, Vencovsky J, Rubbert-Roth A, Mysler E, Sleeman MA, Godwood A, Sinibaldi D, Guo X, White WI, Wang B, Wu CY, Ryan PC, Close D, Weinblatt ME, investigators EEs (2017) A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis 76(6):1020–1030. https://doi.org/10.1136/annrheumdis-2016-210624 CrossRefPubMed

129.

Weinblatt ME, McInnes IB, Kremer JM, Miranda P, Vencovsky J, Guo X, White WI, Ryan PC, Godwood A, Albulescu M, Close D, Burmester GR (2018) A randomized phase IIb study of Mavrilimumab and Golimumab in rheumatoid arthritis. Arthritis Rheum 70(1):49–59. https://doi.org/10.1002/art.40323 CrossRef

130.

Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, Rivas E, Tsai TF, Wasel N, Tyring S, Salko T, Hampele I, Notter M, Karpov A, Helou S, Papavassilis C, Group ES, Group FS (2014) Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 371(4):326–338. https://doi.org/10.1056/NEJMoa1314258 CrossRefPubMed

131.

Gordon KB, Leonardi CL, Lebwohl M, Blauvelt A, Cameron GS, Braun D, Erickson J, Heffernan M (2014) A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis. J Am Acad Dermatol 71(6):1176–1182. https://doi.org/10.1016/j.jaad.2014.07.048 CrossRefPubMed

132.

IB MI, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S, Group FS (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 386(9999):1137–1146. https://doi.org/10.1016/S0140-6736(15)61134-5 CrossRef

133.

Mease P, van der Heijde D, Landewe R, Mpofu S, Rahman P, Tahir H, Singhal A, Boettcher E, Navarra S, Meiser K, Readie A, Pricop L, Abrams K (2018) Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis 77(6):890–897. https://doi.org/10.1136/annrheumdis-2017-212687 CrossRefPubMed

134.

Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H, Pricop L, Andersson M, Readie A, Porter B (2017) Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther 19(1):285. https://doi.org/10.1186/s13075-017-1490-y CrossRefPubMedPubMedCentral

135.

Needell JC, Zipris D (2016) The role of the intestinal microbiome in type 1 diabetes pathogenesis. Curr Diab Rep 16(10):89. https://doi.org/10.1007/s11892-016-0781-z CrossRefPubMed

136.

Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T (2015) Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS One 10(9):e0137429. https://doi.org/10.1371/journal.pone.0137429 CrossRefPubMedPubMedCentral

137.

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202. https://doi.org/10.7554/eLife.01202 CrossRefPubMedPubMedCentral

138.

Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, Takeda K (2016) Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheum 68(11):2646–2661. https://doi.org/10.1002/art.39783 CrossRef

139.

Vaahtovuo J, Munukka E, Korkeamaki M, Luukkainen R, Toivanen P (2008) Fecal microbiota in early rheumatoid arthritis. J Rheumatol 35(8):1500–1505PubMed

140.

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J (2015) The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21(8):895–905. https://doi.org/10.1038/nm.3914 CrossRefPubMed

141.

Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827. https://doi.org/10.1016/j.immuni.2010.06.001 CrossRefPubMedPubMedCentral

142.

Marietta EV, Murray JA, Luckey DH, Jeraldo PR, Lamba A, Patel R, Luthra HS, Mangalam A, Taneja V (2016) Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice. Arthritis Rheum 68(12):2878–2888. https://doi.org/10.1002/art.39785 CrossRef

143.

Yang Z, Fujii H, Mohan SV, Goronzy JJ, Weyand CM (2013) Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J Exp Med 210(10):2119–2134. https://doi.org/10.1084/jem.20130252 CrossRefPubMedPubMedCentral

144.

Shen Y, Wen Z, Li Y, Matteson EL, Hong J, Goronzy JJ, Weyand CM (2017) Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells. Nat Immunol 18(9):1025–1034. https://doi.org/10.1038/ni.3808 CrossRefPubMedPubMedCentral

145.

Yang Z, Shen Y, Oishi H, Matteson EL, Tian L, Goronzy JJ, Weyand CM (2016) Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci Transl Med 8(331):331ra338. https://doi.org/10.1126/scitranslmed.aad7151 CrossRef

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The pathogenicity of Th17 cells in autoimmune diseases

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2019

CD8+ T cell exhaustion

The role of invariant T cells in inflammation of the skin and airways

The immunopathology of lung fibrosis: amphiregulin-producing pathogenic memory T helper-2 cells control the airway fibrotic responses by inducing eosinophils to secrete osteopontin

Regulation of T cell differentiation and function by epigenetic modification enzymes