Abstract
CD4+ T helper cells are classical but constantly reinterpreted T-cell subset, playing critical roles in a diverse range of inflammatory responses or diseases. Depending on the cytokines they release and the immune responses they mediate, CD4+ T cells are classically divided into two major cell populations: Th1 and Th2 cells. However, recent studies challenged this Th1/Th2 paradigm by discovering several T-helper cell subsets with specific differentiation program and functions, including Th17 cells, Treg cells, and Tfh cells. In this chapter, we summarize the current understanding and recent progresses on the Th17 lineage differentiation and its effector impacts on variety of inflammatory responses or disease pathogenesis.
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References
Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8(9):942–949. doi:10.1038/ni1496
Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278(3):1910–1914. doi:10.1074/jbc.M207577200
Al-Ramli W, Prefontaine D, Chouiali F, Martin JG, Olivenstein R, Lemiere C, Hamid Q (2009) T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 123(5):1185–1187. doi:10.1016/j.jaci.2009.02.024
Albanesi C, Cavani A, Girolomoni G (1999) IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. Journal of immunology 162(1):494–502
Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, De Benedetti F, Poli V, Ciliberto G (1998) Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 187(4):461–468
Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129(3):969–984. doi:10.1053/j.gastro.2005.06.071
Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204(8):1849–1861. doi:10.1084/jem.20070663
Ansel KM, Lee DU, Rao A (2003) An epigenetic view of helper T cell differentiation. Nat Immunol 4(7):616–623. doi:10.1038/ni0703-616
Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K, Takeda K (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808–812. doi:10.1038/nature07240
Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK (2008) IL-22 mediates mucosal host defense against gram-negative bacterial pneumonia. Nat Med 14(3):275–281. doi:10.1038/nm1710
Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, Sturton G, Wong SH, McKenzie AN (2007) Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 120(6):1324–1331. doi:10.1016/j.jaci.2007.07.051
Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Consortium NIG, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Belgian-French IBDC, Wellcome Trust Case Control C, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40(8):955–962. doi:10.1038/ng.175
Batten M, Li J, Yi S, Kljavin NM, Danilenko DM, Lucas S, Lee J, de Sauvage FJ, Ghilardi N (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 7(9):929–936. doi:10.1038/ni1375
Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11(9):372–377
Bending D, De la Pena H, Veldhoen M, Phillips JM, Uyttenhove C, Stockinger B, Cooke A (2009) Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 119(3):565–572. doi:10.1172/JCI37865
Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238. doi:10.1038/nature04753
Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK (2004) Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 200(1):79–87. doi:10.1084/jem.20031819
Beyeen AD, Adzemovic MZ, Ockinger J, Stridh P, Becanovic K, Laaksonen H, Lassmann H, Harris RA, Hillert J, Alfredsson L, Celius EG, Harbo HF, Kockum I, Jagodic M, Olsson T (2010) IL-22RA2 associates with multiple sclerosis and macrophage effector mechanisms in experimental neuroinflammation. Journal of immunology 185(11):6883–6890. doi:10.4049/jimmunol.1001392
Brand DD, Latham KA, Rosloniec EF (2007) Collagen-induced arthritis. Nat Protoc 2(5):1269–1275. doi:10.1038/nprot.2007.173
Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J (2006) IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 290(4):G827–838. doi:10.1152/ajpgi.00513.2005
Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C, Yu P, Arpaia E, Mak TW, Kamradt T, Lohoff M (2007) The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8(9):958–966. doi:10.1038/ni1500
Bulek K, Liu C, Swaidani S, Wang L, Page RC, Gulen MF, Herjan T, Abbadi A, Qian W, Sun D, Lauer M, Hascall V, Misra S, Chance MR, Aronica M, Hamilton T, Li X (2011) The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol 12(9):844–852. doi:10.1038/ni.2080
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80(2):273–290. doi:10.1086/511051
Carmi Y, Rinott G, Dotan S, Elkabets M, Rider P, Voronov E, Apte RN (2011) Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis. J immunol 186(6):3462–3471. doi:10.4049/jimmunol.1002901
Chae WJ, Bothwell AL (2011) IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochem Biophys Res Commun 414(1):31–36. doi:10.1016/j.bbrc.2011.09.016
Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL (2010) Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 107(12):5540–5544. doi:10.1073/pnas.0912675107
Chang SH, Park H, Dong C (2006) Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem 281(47):35603–35607. doi:10.1074/jbc.C600256200
Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C (2011) Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 35(4):611–621. doi:10.1016/j.immuni.2011.09.010
Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB (2008) IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity 29(6):899–911. doi:10.1016/j.immuni.2008.10.011
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4 + CD25- naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875–1886. doi:10.1084/jem.20030152
Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O’Shea JJ (2006) Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA 103(21):8137–8142. doi:10.1073/pnas.0600666103
Cheng F, Guo Z, Xu H, Yan D, Li Q (2009) Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 68(4):604–606. doi:10.1136/ard.2008.097089
Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D (1995) Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science 267(5203):1494–1498
Chiricozzi A, Guttman-Yassky E, Suarez-Farinas M, Nograles KE, Tian S, Cardinale I, Chimenti S, Krueger JG (2011) Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131(3):677–687. doi:10.1038/jid.2010.340
Chitnis T, Najafian N, Benou C, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ (2001) Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 108(5):739–747. doi:10.1172/JCI12563
Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, Dong C (2009) Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30(4):576–587. doi:10.1016/j.immuni.2009.02.007
Ciccacci C, Biancone L, Di Fusco D, Ranieri M, Condino G, Giardina E, Onali S, Lepre T, Pallone F, Novelli G, Borgiani P (2012) TRAF3IP2 gene is associated with cutaneous extraintestinal manifestations in Inflammatory Bowel Disease. J Crohns Colitis. doi:10.1016/j.crohns.2012.02.020
Claudio E, Sonder SU, Saret S, Carvalho G, Ramalingam TR, Wynn TA, Chariot A, Garcia-Perganeda A, Leonardi A, Paun A, Chen A, Ren NY, Wang H, Siebenlist U (2009) The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation. J immunol 182(3):1617–1630
Cobb BS, Nesterova TB, Thompson E, Hertweck A, O’Connor E, Godwin J, Wilson CB, Brockdorff N, Fisher AG, Smale ST, Merkenschlager M (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201(9):1367–1373. doi:10.1084/jem.20050572
Conforti-Andreoni C, Spreafico R, Qian HL, Riteau N, Ryffel B, Ricciardi-Castagnoli P, Mortellaro A (2011) Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18. J immunol 187(11):5842–5850. doi:10.4049/jimmunol.1101408
Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, Powrie F (2007) A functionally specialized population of mucosal CD103 + DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204(8):1757–1764. doi:10.1084/jem.20070590
Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI (2008) Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J immunol 180(11):7097–7101
Crispin JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, Kyttaris VC, Juang YT, Tsokos GC (2008) Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J immunol 181(12):8761–8766
Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744–748. doi:10.1038/nature01355
Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10(7):479–489. doi:10.1038/nri2800
Cui G, Qin X, Wu L, Zhang Y, Sheng X, Yu Q, Sheng H, Xi B, Zhang JZ, Zang YQ (2011) Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest 121(2):658–670. doi:10.1172/JCI42974
da Rocha LF, Jr., Duarte AL, Dantas AT, Mariz HA, Pitta Ida R, Galdino SL, Pitta MG (2012) Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity. J Rheumatol 39(7):1320–1325. doi:10.3899/jrheum.111027
Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G (2009) Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 206(11):2407–2416. doi:10.1084/jem.20082286
de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, Feinberg J, von Bernuth H, Samarina A, Janniere L, Fieschi C, Stephan JL, Boileau C, Lyonnet S, Jondeau G, Cormier-Daire V, Le Merrer M, Hoarau C, Lebranchu Y, Lortholary O, Chandesris MO, Tron F, Gambineri E, Bianchi L, Rodriguez-Gallego C, Zitnik SE, Vasconcelos J, Guedes M, Vitor AB, Marodi L, Chapel H, Reid B, Roifman C, Nadal D, Reichenbach J, Caragol I, Garty BZ, Dogu F, Camcioglu Y, Gulle S, Sanal O, Fischer A, Abel L, Stockinger B, Picard C, Casanova JL (2008) Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med 205(7):1543–1550. doi:10.1084/jem.20080321
De Luca A, Zelante T, D’Angelo C, Zagarella S, Fallarino F, Spreca A, Iannitti RG, Bonifazi P, Renauld JC, Bistoni F, Puccetti P, Romani L (2010) IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol 3(4):361–373. doi:10.1038/mi.2010.22
Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao B, Worley PF, Powell JD (2011) The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 12(4):295–303. doi:10.1038/ni.2005
Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. doi:10.1146/annurev.immunol.021908.132612
Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM (2007) Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 8(2):145–153. doi:10.1038/ni1424
Doe C, Bafadhel M, Siddiqui S, Desai D, Mistry V, Rugman P, McCormick M, Woods J, May R, Sleeman MA, Anderson IK, Brightling CE (2010) Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 138(5):1140–1147. doi:10.1378/chest.09-3058
Dong G, Ye R, Shi W, Liu S, Wang T, Yang X, Yang N, Yu X (2003) IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chin Med J 116(4):543–548
Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10(12):1252–1259. doi:10.1038/ni.1798
Du J, Huang C, Zhou B, Ziegler SF (2008) Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3. J Immunol 180(7):4785–4792
Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463. doi:10.1126/science.1135245
Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O’Shea JJ (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32(5):605–615. doi:10.1016/j.immuni.2010.05.003
Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, Belouchi M, Fournier H, Reinhard C, Ding J, Li Y, Tejasvi T, Gudjonsson J, Stoll SW, Voorhees JJ, Lambert S, Weidinger S, Eberlein B, Kunz M, Rahman P, Gladman DD, Gieger C, Wichmann HE, Karlsen TH, Mayr G, Albrecht M, Kabelitz D, Mrowietz U, Abecasis GR, Elder JT, Schreiber S, Weichenthal M, Franke A (2010) Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 42(11):991–995. doi:10.1038/ng.689
Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A, Shapiro AM (2009) Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58(6):1302–1311. doi:10.2337/db08-1113
Endo Y, Iwamura C, Kuwahara M, Suzuki A, Sugaya K, Tumes DJ, Tokoyoda K, Hosokawa H, Yamashita M, Nakayama T (2011) Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3. Immunity 35(5):733–745. doi:10.1016/j.immuni.2011.08.017
Eshima K, Chiba S, Suzuki H, Kokubo K, Kobayashi H, Iizuka M, Iwabuchi K, Shinohara N (2012) Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4(+) Th cells cytotoxic by activating both perforin- and FasL-pathways. Immunol Lett 144(1–2):7–15. doi:10.1016/j.imlet.2012.02.013
Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, McIlgorm A, Jolin HE, McKenzie AN (2006) Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med 203(4):1105–1116. doi:10.1084/jem.20051615
Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, Ohsugi Y, Nishikawa T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis Rheum 58(12):3710–3719. doi:10.1002/art.24126
Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52(1):65–70
Furlan R, Martino G, Galbiati F, Poliani PL, Smiroldo S, Bergami A, Desina G, Comi G, Flavell R, Su MS, Adorini L (1999) Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J Immunol 163(5):2403–2409
Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9(8):556–567. doi:10.1038/nri2586
Garg AV, Ahmed M, Vallejo AN, Ma A, Gaffen SL (2013) The deubiquitinase a20 mediates feedback inhibition of interleukin-17 receptor signaling. Science Signal 6(278):ra44. doi:10.1126/scisignal.2003699
Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445(7129):771–775. doi:10.1038/nature05543
Geboes L, Dumoutier L, Kelchtermans H, Schurgers E, Mitera T, Renauld JC, Matthys P (2009) Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum 60(2):390–395. doi:10.1002/art.24220
Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Mazurov V, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Mpofu S (2013) Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 72(6):863–869. doi:10.1136/annrheumdis-2012-201601
Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, Sloan-Lancaster J (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62(4):929–939. doi:10.1002/art.27334
Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O’Shea JJ (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467(7318):967–971. doi:10.1038/nature09447
Gopal M, da Cunha AP, Weiner HL (2013) 97: Silencing MicroRNA-21 ameliorates Th17 mediated autoimmune inflammation. Cytokine 63(3):266
Gordon SM, Carty SA, Kim JS, Zou T, Smith-Garvin J, Alonzo ES, Haimm E, Sant’Angelo DB, Koretzky GA, Reiner SL, Jordan MS (2011) Requirements for eomesodermin and promyelocytic leukemia zinc finger in the development of innate-like CD8 + T cells. J Immunol 186(8):4573–4578. doi:10.4049/jimmunol.1100037
Gorelik L, Fields PE, Flavell RA (2000) Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. J Immunol 165(9):4773–4777
Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A (2002) IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol 169(12):7104–7110
Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, Huang M, Schneider M, Miller SD, Ting JP (2010) NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol 185(2):974–981. doi:10.4049/jimmunol.0904145
Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491(7423):254–258 nature11465 [pii]10.10348/nature11465
Gulen MF, Bulek K, Xiao H, Yu M, Gao J, Sun L, Beurel E, Kaidanovich-Beilin O, Fox PL, DiCorleto PE, Wang JA, Qin J, Wald DN, Woodgett JR, Jope RS, Carman J, Dongre A, Li X (2012) Inactivation of the enzyme GSK3alpha by the kinase IKKi promotes AKT-mTOR signaling pathway that mediates interleukin-1-induced Th17 cell maintenance. Immunity 37(5):800–812. doi:10.1016/j.immuni.2012.08.019
Gulen MF, Kang Z, Bulek K, Youzhong W, Kim TW, Chen Y, Altuntas CZ, Sass Bak-Jensen K, McGeachy MJ, Do JS, Xiao H, Delgoffe GM, Min B, Powell JD, Tuohy VK, Cua DJ, Li X (2010) The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity 32(1):54–66. doi:10.1016/j.immuni.2009.12.003
Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466(7308):835–840. doi:10.1038/nature09267
Gutcher I, Donkor MK, Ma Q, Rudensky AY, Flavell RA, Li MO (2011) Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity 34(3):396–408. doi:10.1016/j.immuni.2011.03.005
Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Hacker G, Mann M, Karin M (2006) Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439(7073):204–207. doi:10.1038/nature04369
Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, Purdy D, Fitch E, Iordanov M, Blauvelt A (2009) Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129(9):2175–2183. doi:10.1038/jid.2009.65
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6(11):1123–1132. doi:10.1038/ni1254
Harris TJ, Grosso JF, Yen HR, Xin H, Kortylewski M, Albesiano E, Hipkiss EL, Getnet D, Goldberg MV, Maris CH, Housseau F, Yu H, Pardoll DM, Drake CG (2007) Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 179(7):4313–4317
Hartupee J, Liu C, Novotny M, Sun D, Li X, Hamilton TA (2009) IL-17 signaling for mRNA stabilization does not require TNF receptor-associated factor 6. J Immunol 182(3):1660–1666
Hata H, Sakaguchi N, Yoshitomi H, Iwakura Y, Sekikawa K, Azuma Y, Kanai C, Moriizumi E, Nomura T, Nakamura T, Sakaguchi S (2004) Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 114(4):582–588. doi:10.1172/JCI21795
He D, Li H, Yusuf N, Elmets CA, Athar M, Katiyar SK, Xu H (2012) IL-17 mediated inflammation promotes tumor growth and progression in the skin. PLoS ONE 7(2):e32126. doi:10.1371/journal.pone.0032126
He JQ, Zarnegar B, Oganesyan G, Saha SK, Yamazaki S, Doyle SE, Dempsey PW, Cheng G (2006) Rescue of TRAF3-null mice by p100 NF-kappa B deficiency. J Exp Med 203(11):2413–2418 (jem.20061166 [pii]/jem.20061166)
He YW, Deftos ML, Ojala EW, Bevan MJ (1998) RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells. Immunity 9(6):797–806
Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(Pt 1):1–20. doi:10.1042/BJ20030407
Hemdan NY, Birkenmeier G, Wichmann G (2012) Key molecules in the differentiation and commitment program of T helper 17 (Th17) cells up-to-date. Immunol Lett 148(2):97–109. doi:10.1016/j.imlet.2012.09.007
Herjan T, Yao P, Qian W, Li X, Liu C, Bulek K, Sun D, Yang WP, Zhu J, He A, Carman JA, Erzurum SC, Lipshitz HD, Fox PL, Hamilton TA, Li X (2013) HuR Is Required for IL-17-Induced Act1-Mediated CXCL1 and CXCL5 mRNA Stabilization. J Immunol. doi:10.4049/jimmunol.1203315
Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M et al (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18(11):1797–1801. doi:10.1002/eji.1830181122
Ho AW, Shen F, Conti HR, Patel N, Childs EE, Peterson AC, Hernandez-Santos N, Kolls JK, Kane LP, Ouyang W, Gaffen SL (2010) IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail. J Immunol 185(2):1063–1070 jimmunol.0903739 [pii]/jimmunol.0903739
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357(16):1608–1619. doi:10.1056/NEJMoa073687
Hu Y, Ota N, Peng I, Refino CJ, Danilenko DM, Caplazi P, Ouyang W (2010) IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 184(8):4307–4316. doi:10.4049/jimmunol.0903614
Huang F, Kao CY, Wachi S, Thai P, Ryu J, Wu R (2007) Requirement for both JAK-mediated PI3 K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol 179(10):6504–6513
Huber M, Brustle A, Reinhard K, Guralnik A, Walter G, Mahiny A, von Low E, Lohoff M (2008) IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci USA 105(52):20846–20851. doi:10.1073/pnas.0809077106
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Psoriasis Study G, Durez P, Tak PP, Gomez-Reino JJ, Rheumatoid Arthritis Study G, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Uveitis Study G, Rose K, Haider A, Di Padova F (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Science translational medicine 2 (52):52ra72. doi:10.1126/scitranslmed.3001107
Huffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, Juneblad K, Apel M, McManus R, Ho P, Bruce IN, Ryan AW, Behrens F, Lascorz J, Bohm B, Traupe H, Lohmann J, Gieger C, Wichmann HE, Herold C, Steffens M, Klareskog L, Wienker TF, Fitzgerald O, Alenius GM, McHugh NJ, Novelli G, Burkhardt H, Barton A, Reis A (2010) Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 42(11):996–999. doi:10.101038/ng.688
Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, Menon S, Seymour B, Jackson C, Kung TT, Brieland JK, Zurawski SM, Chapman RW, Zurawski G, Coffman RL (2002) New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 169(1):443–453
Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY (2012) Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 33(4):931–936. doi:10.1093/carcin/bgs106
Ichiyama K, Hashimoto M, Sekiya T, Nakagawa R, Wakabayashi Y, Sugiyama Y, Komai K, Saba I, Moroy T, Yoshimura A (2009) Gfi1 negatively regulates T(h)17 differentiation by inhibiting RORgammat activity. Int Immunol 21(7):881–889. doi:10.1093/intimm/dxp054
Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, Yoshimura A (2011) Transcription factor Smad-independent T helper 17 cell induction by transforming-growth factor-beta is mediated by suppression of eomesodermin. Immunity 34(5):741–754. doi:10.1016/j.immuni.2011.02.021
Inoue M, Williams KL, Gunn MD, Shinohara ML (2012) NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 109(26):10480–10485. doi:10.1073/pnas.1201836109
Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30(1):108–119. doi:10.1016/j.immuni.2008.11.009
Ito A, Bebo BF Jr, Matejuk A, Zamora A, Silverman M, Fyfe-Johnson A, Offner H (2001) Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J Immunol 167(1):542–552
Ito R, Kita M, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Iwakura Y, Okanoue T, Yoshikawa T, Kataoka K, Mazda O (2008) Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. Biochem Biophys Res Commun 377(1):12–16. doi:10.1016/j.bbrc.2008.09.019
Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485–498. doi:10.1016/j.cell.2009.09.033
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17 + T helper cells. Cell 126(6):1121–1133. doi:10.1016/j.cell.2006.07.035
Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34(2):149–162. doi:10.1016/j.immuni.2011.02.012
Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, Chen VS, Gris D, Matsushima GK, Ting JP (2010) The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci 30(47):15811–15820. doi:10.1523/JNEUROSCI.4088-10.2010
Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, Gao Y, Yao A, Wang X, Yu L, Sun B (2013) IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer 13:59. doi:10.1186/1471-2407-13-59
Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K (2009) Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 160(2):319–324. doi:10.1111/j.1365-2133.2008.08902.x
Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, Chen CS, Fu W, Gudjonsson JE, McCormick TS, Ward NL (2013) Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol 190(5):2252–2262. doi:10.4049/jimmunol.1201505
Joosten LA, Helsen MM, van de Loo FA, van den Berg WB (2008) Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFalpha, anti-IL-1alpha/beta and IL-1Ra. Arthritis Rheum 58(2 Suppl):S110–122. doi:10.1002/art.23363
Kang Z, Swaidani S, Yin W, Wang C, Barlow JL, Gulen MF, Bulek K, Do JS, Aronica M, McKenzie AN, Min B, Li X (2012) Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(−)c-Kit(+) innate cell population. Immunity 36(5):821–833. doi:10.1016/j.immuni.2012.03.021
Kawaguchi M, Kokubu F, Matsukura S, Ieki K, Odaka M, Watanabe S, Suzuki S, Adachi M, Huang SK (2003) Induction of C-X-C chemokines, growth-related oncogene alpha expression, and epithelial cell-derived neutrophil-activating protein-78 by ML-1 (interleukin-17F) involves activation of Raf1-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 pathway. J Pharmacology and experimental therapeutics 307(3):1213–1220. doi:10.1124/jpet.103.056341
Kim MR, Manoukian R, Yeh R, Silbiger SM, Danilenko DM, Scully S, Sun J, DeRose ML, Stolina M, Chang D, Van GY, Clarkin K, Nguyen HQ, Yu YB, Jing S, Senaldi G, Elliott G, Medlock ES (2002) Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Blood 100(7):2330–2340. doi:10.1182/blood-2002-01-0012
Kirigin FF, Lindstedt K, Sellars M, Ciofani M, Low SL, Jones L, Bell F, Pauli F, Bonneau R, Myers RM, Littman DR, Chong MM (2012) Dynamic microRNA gene transcription and processing during T cell development. J Immunol 188(7):3257–3267. doi:10.4049/jimmunol.1103175
Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA (2013) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496(7446):518–522. doi:10.1038/nature11868
Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM, Blumenschein WM, McClanahan T, Brombacher F, Hurst SD, Kastelein RA, Cua DJ (2007) IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 204(1):161–170. doi:10.1084/jem.20061738
Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, Sudo K, Iwakura Y (2006) IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177(1):566–573
Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, Oukka M, Kuchroo VK (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152):484–487. doi:10.1038/nature05970
Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517. doi:10.1146/annurev.immunol.021908.132710
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103(9):1345–1352. doi:10.1172/JCI5703
Krajewski S, Zapata JM, Krajewska M, VanArsdale T, Shabaik A, Gascoyne RD, Reed JC (1997) Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family. J Immunol 159(12):5841–5852
Krakowski M, Owens T (1996) Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur J Immunol 26(7):1641–1646. doi:10.1002/eji.1830260735
Krawczyk CM, Shen H, Pearce EJ (2007) Functional plasticity in memory T helper cell responses. J Immunol 178(7):4080–4088
Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B (2007) IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 179(12):8098–8104
Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149. doi:10.1182/blood-2009-03-208249
Kryczek I, Wei S, Szeliga W, Vatan L, Zou W (2009) Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114(2):357–359. doi:10.1182/blood-2008-09-177360
Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D (2012) IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med 18(4):547–554. doi:10.1038/nm.2684
Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL, Aujla SJ, Reardon B, Moore M, Shea P, Schreckhise R, Bukowski TR, Presnell S, Guerra-Lewis P, Parrish-Novak J, Ellsworth JL, Jaspers S, Lewis KE, Appleby M, Kolls JK, Rixon M, West JW, Gao Z, Levin SD (2007) Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol 179(8):5462–5473
Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA, Dienger K, Budelsky AL, Wills-Karp M (2010) Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol 11(10):928–935. doi:10.1038/ni.1926
Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH (2011) Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity. J Immunol 186(10):5738–5748. doi:10.4049/jimmunol.1003597
Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006) IL-23 promotes tumour incidence and growth. Nature 442(7101):461–465. doi:10.1038/nature04808
Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201(2):233–240. doi:10.1084/jem.20041257
Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. doi:10.1016/j.cell.2012.03.017
Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O’Shea JJ (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26(3):371–381. doi:10.1016/j.immuni.2007.02.009
Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH (2011) T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat. Nat Immunol 12(1):96–104. doi:10.1038/ni.1969
Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA, Boothby M (2010) Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32(6):743–753. doi:10.1016/j.immuni.2010.06.002
Lee YK, Turner H, Maynard CL, Oliver JR, Chen D, Elson CO, Weaver CT (2009) Late developmental plasticity in the T helper 17 lineage. Immunity 30(1):92–107. doi:10.1016/j.immuni.2008.11.005
Leonard JP, Waldburger KE, Goldman SJ (1995) Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J Exp Med 181(1):381–386
Lexberg MH, Taubner A, Forster A, Albrecht I, Richter A, Kamradt T, Radbruch A, Chang HD (2008) Th memory for interleukin-17 expression is stable in vivo. Eur J Immunol 38(10):2654–2664. doi:10.1002/eji.200838541
Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, Dowd P, Gurney AL, Wood WI (2000) Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci USA 97(2):773–778
Li MO, Flavell RA (2008) TGF-beta: a master of all T cell trades. Cell 134(3):392–404. doi:10.1016/j.cell.2008.07.025
Li MO, Sanjabi S, Flavell RA (2006) Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25(3):455–471. doi:10.1016/j.immuni.2006.07.011
Li MO, Wan YY, Flavell RA (2007) T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26(5):579–591. doi:10.1016/j.immuni.2007.03.014
Li Q, Han Y, Fei G, Guo Z, Ren T, Liu Z (2012) IL-17 promoted metastasis of non-small-cell lung cancer cells. Immunol Lett 148(2):144–150. doi:10.1016/j.imlet.2012.10.011
Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203(10):2271–2279. doi:10.1084/jem.20061308
Lin Y, Ritchea S, Logar A, Slight S, Messmer M, Rangel-Moreno J, Guglani L, Alcorn JF, Strawbridge H, Park SM, Onishi R, Nyugen N, Walter MJ, Pociask D, Randall TD, Gaffen SL, Iwakura Y, Kolls JK, Khader SA (2009) Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 31(5):799–810. doi:10.1016/j.immuni.2009.08.025
Liu C, Qian W, Qian Y, Giltiay NV, Lu Y, Swaidani S, Misra S, Deng L, Chen ZJ, Li X (2009) Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Science signaling 2(92):ra63. doi:10.1126/scisignal.2000382
Liu C, Swaidani S, Qian W, Kang Z, Sun P, Han Y, Wang C, Gulen MF, Yin W, Zhang C, Fox PL, Aronica M, Hamilton TA, Misra S, Deng J, Li X (2011) A CC’ loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Science signaling 4(197):ra72. doi:10.1126/scisignal.2001843
Liu SM, King C (2013) IL-21-producing Th cells in immunity and autoimmunity. Journal of immunology 191(7):3501–3506. doi:10.4049/jimmunol.1301454
Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I, Kwok PY, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4(3):e1000041. doi:10.1371/journal.pgen.1000041
Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8(5):500–508. doi:10.1038/nm0502-500
Lohoff M, Mittrucker HW, Prechtl S, Bischof S, Sommer F, Kock S, Ferrick DA, Duncan GS, Gessner A, Mak TW (2002) Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4. Proc Natl Acad Sci USA 99(18):11808–11812. doi:10.1073/pnas.182425099
Lubberts E, Joosten LA, van de Loo FA, Schwarzenberger P, Kolls J, van den Berg WB (2002) Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflam Res off J Eur Histamine Res Soc 51(2):102–104
Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50(2):650–659. doi:10.1002/art.20001
Luthje K, Kallies A, Shimohakamada Y, Belz GT, Light A, Tarlinton DM, Nutt SL (2012) The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat Immunol 13(5):491–498. doi:10.1038/ni.2261
Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, Fulcher DA, Tangye SG, Cook MC (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205(7):1551–1557. doi:10.1084/jem.20080218
Ma F, Xu S, Liu X, Zhang Q, Xu X, Liu M, Hua M, Li N, Yao H, Cao X (2011) The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma. Nat Immunol 12(9):861–869. doi:10.1038/ni.2073
Ma J, Wang R, Fang X, Ding Y, Sun Z (2011) Critical role of TCF-1 in repression of the IL-17 gene. PLoS ONE 6(9):e24768. doi:10.1371/journal.pone.0024768
Ma Y, Thornton S, Boivin GP, Hirsh D, Hirsch R, Hirsch E (1998) Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum 41(10):1798–1805. doi:10.1002/1529-0131(199810)41:10<1798::AID-ART11>3.0.CO;2-L
Maitra A, Shen F, Hanel W, Mossman K, Tocker J, Swart D, Gaffen SL (2007) Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc Natl Acad Sci USA 104(18):7506–7511. doi:10.1073/pnas.0611589104
Male V, Nisoli I, Gascoyne DM, Brady HJ (2012) E4BP4: an unexpected player in the immune response. Trends Immunol 33(2):98–102. doi:10.1016/j.it.2011.10.002
Malfait AM, Butler DM, Presky DH, Maini RN, Brennan FM, Feldmann M (1998) Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clin Exp Immunol 111(2):377–383
Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9(6):641–649. doi:10.1038/ni.1610
Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441(7090):231–234. doi:10.1038/nature04754
Marie JC, Letterio JJ, Gavin M, Rudensky AY (2005) TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+ CD25+ regulatory T cells. J Exp Med 201(7):1061–1067. doi:10.1084/jem.20042276
Marijnissen RJ, Koenders MI, Smeets RL, Stappers MH, Nickerson-Nutter C, Joosten LA, Boots AM, van den Berg WB (2011) Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation. Arthritis Rheum 63(10):2939–2948. doi:10.1002/art.30469
Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787–798. doi:10.1016/j.immuni.2009.09.014
Mathur AN, Chang HC, Zisoulis DG, Kapur R, Belladonna ML, Kansas GS, Kaplan MH (2006) T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood 108(5):1595–1601. doi:10.1182/blood-2006-04-015016
Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, O’Malley JT, Kapur R, Levy DE, Kansas GS, Kaplan MH (2007) Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178(8):4901–4907
McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397. doi:10.1038/ni1539
Medvedev A, Chistokhina A, Hirose T, Jetten AM (1997) Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene. Genomics 46(1):93–102. doi:10.1006/geno.1997.4980
Mellett M, Atzei P, Horgan A, Hams E, Floss T, Wurst W, Fallon PG, Moynagh PN (2012) Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia. Nat Commun 3:1119. doi:10.1038/ncomms2127
Meng G, Zhang F, Fuss I, Kitani A, Strober W (2009) A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30(6):860–874. doi:10.1016/j.immuni.2009.04.012
Merkenschlager M, Wilson CB (2008) RNAi and chromatin in T cell development and function. Curr Opin Immunol 20(2):131–138. doi:10.1016/j.coi.2008.03.013
Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O’Shea J, Holland SM, Paul WE, Douek DC (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452(7188):773–776. doi:10.1038/nature06764
Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448(7157):1058–1062. doi:10.1038/nature06096
Mohawk JA, Green CB, Takahashi JS (2012) Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445–462. doi:10.1146/annurev-neuro-060909-153128
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, Olivenstein R, Elias J, Chakir J (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108(3):430–438. doi:10.1067/mai.2001.117929
Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173. doi:10.1146/annurev.iy.07.040189.001045
Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317(5835):256–260. doi:10.1126/science.1145697
Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202(2):261–269. doi:10.1084/jem.20050678
Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198(12):1951–1957. doi:10.1084/jem.20030896
Murphy E, Shibuya K, Hosken N, Openshaw P, Maino V, Davis K, Murphy K, O’Garra A (1996) Reversibility of T helper 1 and 2 populations is lost after long-term stimulation. J Exp Med 183(3):901–913
Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL (2011) Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol 187(5):2213–2221. doi:10.4049/jimmunol.1003952
Mycko MP, Cichalewska M, Machlanska A, Cwiklinska H, Mariasiewicz M, Selmaj KW (2012) MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination. Proc Natl Acad Sci USA 109(20):E1248–1257. doi:10.1073/pnas.1114325109
Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M, Iwakura Y (2002) Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17(3):375–387
Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6(5):369–381. doi:10.1038/nrc1881
Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman DR, Taniuchi I (2007) Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer. J Exp Med 204(8):1749–1755. doi:10.1084/jem.20062456
Neurath MF, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, Mizoguchi A, Mizoguchi E, Mudter J, Galle PR, Bhan A, Autschbach F, Sullivan BM, Szabo SJ, Glimcher LH, Blumberg RS (2002) The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn’s disease. J Exp Med 195(9):1129–1143
Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Hashimoto J, Azuma J, Kishimoto T (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50(6):1761–1769. doi:10.1002/art.20303
Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, Ramon M, Bergman R, Krueger JG, Guttman-Yassky E (2009) IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 123(6):1244–1252, e1242. doi:10.1016/j.jaci.2009.03.041
Novatchkova M, Leibbrandt A, Werzowa J, Neubuser A, Eisenhaber F (2003) The STIR-domain superfamily in signal transduction, development and immunity. Trends Biochem Sci 28(5):226–229. doi:10.1016/S0968-0004(03)00067-7
Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448(7152):480–483. doi:10.1038/nature05969
Oganesyan G, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, Perry A, Cheng G (2006) Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439(7073):208–211. doi:10.1038/nature04374
Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y (2004) Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol 110(1):55–62. doi:10.1016/j.clim.2003.09.013
Okuda Y, Sakoda S, Bernard CC, Fujimura H, Saeki Y, Kishimoto T, Yanagihara T (1998) IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 10(5):703–708
Oliver JA, Stolberg VR, Chensue SW, King PD (2012) IL-4 acts as a potent stimulator of IFN-gamma expression in CD8 + T cells through STAT6-dependent and independent induction of Eomesodermin and T-bet. Cytokine 57(1):191–199. doi:10.1016/j.cyto.2011.10.006
Onishi RM, Park SJ, Hanel W, Ho AW, Maitra A, Gaffen SL (2010) SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction. J Biol Chem 285(43):32751–32759. doi:10.1074/jbc.M110.121418
Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S (2007) Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446(7136):685–689. doi:10.1038/nature05673
Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13(5):715–725
Ouyang W (2010) Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease. Cytokine Growth Factor Rev 21(6):435–441. doi:10.1016/j.cytogfr.2010.10.007
Owyang AM, Zaph C, Wilson EH, Guild KJ, McClanahan T, Miller HR, Cua DJ, Goldschmidt M, Hunter CA, Kastelein RA, Artis D (2006) Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med 203(4):843–849. doi:10.1084/jem.20051496
Pan G, French D, Mao W, Maruoka M, Risser P, Lee J, Foster J, Aggarwal S, Nicholes K, Guillet S, Schow P, Gurney AL (2001) Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice. J Immunol 167(11):6559–6567
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, Aras G, Li J, Russell CB, Thompson EH, Baumgartner S (2012) Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 366(13):1181–1189. doi:10.1056/NEJMoa1109017
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133–1141. doi:10.1038/ni1261
Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D (2000) Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408(6808):57–63. doi:10.1038/35040504
Pennino D, Bhavsar PK, Effner R, Avitabile S, Venn P, Quaranta M, Marzaioli V, Cifuentes L, Durham SR, Cavani A, Eyerich K, Chung KF, Schmidt-Weber CB, Eyerich S (2013) IL-22 suppresses IFN-gamma-mediated lung inflammation in asthmatic patients. J Allergy Clin Immunol 131(2):562–570. doi:10.1016/j.jaci.2012.09.036
Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M, Lehr HA, Hirth S, Weigmann B, Wirtz S, Ouyang W, Neurath MF, Becker C (2009) STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 206(7):1465–1472. doi:10.1084/jem.20082683
Pisitkun P, Ha HL, Wang H, Claudio E, Tivy CC, Zhou H, Mayadas TN, Illei GG, Siebenlist U (2012) Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity 37(6):1104–1115. doi:10.1016/j.immuni.2012.08.014
Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J, Kordula T, Zhang QW, Vallance B, Swaidani S, Aronica M, Tuohy VK, Hamilton T, Li X (2007) The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol 8(3):247–256. doi:10.1038/ni1439
Qin H, Wang L, Feng T, Elson CO, Niyongere SA, Lee SJ, Reynolds SL, Weaver CT, Roarty K, Serra R, Benveniste EN, Cong Y (2009) TGF-beta promotes Th17 cell development through inhibition of SOCS3. Journal of immunology 183(1):97–105. doi:10.4049/jimmunol.0801986
Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, Jallal B, Yao Y, Shi Y, Qian Y (2012) TRAF6 dependent Act1 phosphorylation by the IKK-related kinases suppresses IL-17-induced NF-kappaB activation. Mol Cell Biol. doi: 10.1128/MCB.00268-12
Qui HZ, Hagymasi AT, Bandyopadhyay S, St Rose MC, Ramanarasimhaiah R, Menoret A, Mittler RS, Gordon SM, Reiner SL, Vella AT, Adler AJ (2011) CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol 187(7):3555–3564. doi:10.4049/jimmunol.1101244
Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J, Hackney J, Kim J, Zhou M, Lai J, Modrusan Z, Sai T, Lee W, Xu M, Caplazi P, Diehl L, de Voss J, Balazs M, Gonzalez L Jr, Singh H, Ouyang W, Pappu R (2011) IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol 12(12):1159–1166. doi:10.1038/ni.2156
Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (2002) Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression. J Exp Med 195(8):1003–1012
Renner ED, Rylaarsdam S, Anover-Sombke S, Rack AL, Reichenbach J, Carey JC, Zhu Q, Jansson AF, Barboza J, Schimke LF, Leppert MF, Getz MM, Seger RA, Hill HR, Belohradsky BH, Torgerson TR, Ochs HD (2008) Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122(1):181–187. doi:10.1016/j.jaci.2008.04.037
Reynolds JM, Martinez GJ, Nallaparaju KC, Chang SH, Wang YH, Dong C (2012) Cutting edge: regulation of intestinal inflammation and barrier function by IL-17C. J Immunol 189(9):4226–4230. doi:10.4049/jimmunol.1103014
Rickel EA, Siegel LA, Yoon BR, Rottman JB, Kugler DG, Swart DA, Anders PM, Tocker JE, Comeau MR, Budelsky AL (2008) Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J Immunol 181(6):4299–4310
Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A (2011) IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. Journal of immunology 186(3):1495–1502. doi:10.4049/jimmunol.1001001
Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316(5824):608–611. doi:10.1126/science.1139253
Ron D, Fuchs Y, Chorev DS (2008) Know thy Sef: a novel class of feedback antagonists of receptor tyrosine kinase signaling. Int J Biochem Cell Biol 40(10):2040–2052. doi:10.1016/j.biocel.2008.03.013
Rouvier E, Luciani MF, Mattei MG, Denizot F, Golstein P (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 150(12):5445–5456
Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, Komatsu R, Miura N, Adachi Y, Ohno N, Shibuya K, Yamamoto N, Kawakami K, Yamasaki S, Saito T, Akira S, Iwakura Y (2010) Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32(5):681–691. doi:10.1016/j.immuni.2010.05.001
Saleh A, Shan L, Halayko AJ, Kung S, Gounni AS (2009) Critical role for STAT3 in IL-17A-mediated CCL11 expression in human airway smooth muscle cells. J Immunol 182(6):3357–3365. doi:10.4049/jimmunol.0801882
Samoilova EB, Horton JL, Hilliard B, Liu TS, Chen Y (1998) IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 161(12):6480–6486
Sarkar S, Zhou X, Justa S, Bommireddy SR (2013) Interleukin-22 reduces the severity of collagen-induced arthritis in association with increased levels of interleukin-10. Arthritis Rheum 65(4):960–971. doi:10.1002/art.37849
Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, Lohse P, Goke B, Brand S (2008) Linking genetic susceptibility to Crohn’s disease with Th17 cell function: IL-22 serum levels are increased in Crohn’s disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis 14(2):204–212. doi:10.1002/ibd.20315
Schnyder B, Lima C, Schnyder-Candrian S (2010) Interleukin-22 is a negative regulator of the allergic response. Cytokine 50(2):220–227. doi:10.1016/j.cyto.2010.02.003
Schulz SM, Kohler G, Schutze N, Knauer J, Straubinger RK, Chackerian AA, Witte E, Wolk K, Sabat R, Iwakura Y, Holscher C, Muller U, Kastelein RA, Alber G (2008) Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. Journal of immunology 181(11):7891–7901
Schwandner R, Yamaguchi K, Cao Z (2000) Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J Exp Med 191(7):1233–1240
Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jurgens M, Schmechel S, Konrad A, Goke B, Ochsenkuhn T, Muller-Myhsok B, Lohse P, Brand S (2008) Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis 14(4):437–445. doi:10.1002/ibd.20339
Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, Tomita S, Imura J, Shiratori K, Chiba T, Fujimori T (2010) Involvement of the IL-22/REG Ialpha axis in ulcerative colitis. Lab Invest J Tech Methods pathol 90(3):496–505. doi:10.1038/labinvest.2009.147
Serada S, Fujimoto M, Mihara M, Koike N, Ohsugi Y, Nomura S, Yoshida H, Nishikawa T, Terabe F, Ohkawara T, Takahashi T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105(26):9041–9046. doi:10.1073/pnas.0802218105
Shaw PJ, Lukens JR, Burns S, Chi H, McGargill MA, Kanneganti TD (2010) Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. J Immunol 184(9):4610–4614. doi:10.4049/jimmunol.1000217
Shen F, Li N, Gade P, Kalvakolanu DV, Weibley T, Doble B, Woodgett JR, Wood TD, Gaffen SL (2009) IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain. Science signaling 2(59):ra8. doi:10.1126/scisignal.2000066
Shi P, Zhu S, Lin Y, Liu Y, Liu Y, Chen Z, Shi Y, Qian Y (2011) Persistent stimulation with interleukin-17 desensitizes cells through SCFbeta-TrCP-mediated degradation of Act1. Sci Signal 4(197):ra73. doi:10.1126/scisignal.2001653
Smith KM, Guerau-de-Arellano M, Costinean S, Williams JL, Bottoni A, Mavrikis Cox G, Satoskar AR, Croce CM, Racke MK, Lovett-Racke AE, Whitacre CC (2012) miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. Journal of immunology 189(4):1567–1576. doi:10.4049/jimmunol.1103171
Sonder SU, Saret S, Tang W, Sturdevant DE, Porcella SF, Siebenlist U (2011) IL-17-induced NF-kappaB activation via CIKS/Act1: physiologic significance and signaling mechanisms. J Biol Chem 286(15):12881–12890. doi:10.1074/jbc.M110.199547
Sonderegger I, Kisielow J, Meier R, King C, Kopf M (2008) IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol 38(7):1833–1838. doi:10.1002/eji.200838511
Song X, Gao H, Lin Y, Yao Y, Zhu S, Wang J, Liu Y, Yao X, Meng G, Shen N, Shi Y, Iwakura Y, Qian Y (2014) Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity 40(1):140–152. doi:10.1016/j.immuni.2013.11.018
Song X, Qian Y (2013) The activation and regulation of IL-17 receptor mediated signaling. Cytokine 62(2):175–182. doi:10.1016/j.cyto.2013.03.014
Song X, Qian Y (2013) IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases. Cell Signal 25(12):2335–2347. doi:10.1016/j.cellsig.2013.07.021
Song X, Zhu S, Shi P, Liu Y, Shi Y, Levin SD, Qian Y (2011) IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nat Immunol 12(12):1151–1158. doi:10.1038/ni.2155
Staal FJ, Luis TC, Tiemessen MM (2008) WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 8(8):581–593. doi:10.1038/nri2360
Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, Matloubian M, Blelloch R, Ansel KM (2011) MicroRNA-29 regulates T-box transcription factors and interferon-gamma production in helper T cells. Immunity 35(2):169–181. doi:10.1016/j.immuni.2011.07.009
Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Huffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mossner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Stahle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42(11):985–990. doi:10.1038/ng.694
Stromnes IM, Goverman JM (2006) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1(4):1810–1819. doi:10.1038/nprot.2006.285
Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O’Shea JJ, Hennighausen L, Ernst M, Hunter CA (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7(9):937–945. doi:10.1038/ni1376
Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, Fujiyama Y, Andoh A (2010) The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol 160(3):386–393. doi:10.1111/j.1365-2249.2010.04093.x
Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, Blumberg RS, Xavier RJ, Mizoguchi A (2008) IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 118(2):534–544. doi:10.1172/JCI33194
Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204(8):1775–1785. doi:10.1084/jem.20070602
Sun D, Novotny M, Bulek K, Liu C, Li X, Hamilton T (2011) Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF). Nat Immunol 12(9):853–860. doi:10.1038/ni.2081
Suto A, Kashiwakuma D, Kagami S, Hirose K, Watanabe N, Yokote K, Saito Y, Nakayama T, Grusby MJ, Iwamoto I, Nakajima H (2008) Development and characterization of IL-21-producing CD4 + T cells. J Exp Med 205(6):1369–1379. doi:10.1084/jem.20072057
Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC (2006) A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 203(7):1685–1691. doi:10.1084/jem.20060285
Swaidani S, Bulek K, Kang Z, Liu C, Lu Y, Yin W, Aronica M, Li X (2009) The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation. J Immunol 182(3):1631–1640
Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185(5):817–824
Takahashi K, Hirose K, Kawashima S, Niwa Y, Wakashin H, Iwata A, Tokoyoda K, Renauld JC, Iwamoto I, Nakayama T, Nakajima H (2011) IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation. The Journal of allergy and clinical immunology 128(5):1067–1076, e1061–1066. doi:10.1016/j.jaci.2011.06.018
Tamachi T, Maezawa Y, Ikeda K, Kagami S, Hatano M, Seto Y, Suto A, Suzuki K, Watanabe N, Saito Y, Tokuhisa T, Iwamoto I, Nakajima H (2006) IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J Allergy Clin Immunol 118(3):606–614. doi:10.1016/j.jaci.2006.04.051
Teunissen MB, Koomen CW, de Malefyt Waal R, Wierenga EA, Bos JD (1998) Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 111(4):645–649. doi:10.1046/j.1523-1747.1998.00347.x
Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K (2007) Regulation of the germinal center response by microRNA-155. Science 316(5824):604–608. doi:10.1126/science.1141229
Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, Fang W, Xiong B, Wan Y, Dong C (2012) A protective role by interleukin-17F in colon tumorigenesis. PLoS ONE 7(4):e34959. doi:10.1371/journal.pone.0034959
Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, Galon J (2011) Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71(4):1263–1271. doi:10.1158/0008-5472.CAN-10-2907
Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 177(1):36–39
Tran EH, Prince EN, Owens T (2000) IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. J Immunol 164(5):2759–2768
Tschopp J, Martinon F, Burns K (2003) NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 4(2):95–104. doi:10.1038/nrm1019
Tseng PH, Matsuzawa A, Zhang W, Mino T, Vignali DA, Karin M (2009) Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nat Immunol 11(1):70–75. doi:10.1038/ni.1819
Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172(1):146–155. doi:10.2353/ajpath.2008.070690
Van Belle AB, de Heusch M, Lemaire MM, Hendrickx E, Warnier G, Dunussi-Joannopoulos K, Fouser LA, Renauld JC, Dumoutier L (2012) IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice. J Immunol 188(1):462–469. doi:10.4049/jimmunol.1102224
Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278. doi:10.1146/annurev.iy.08.040190.001345
Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453(7191):106–109. doi:10.1038/nature06881
Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179–189. doi:10.1016/j.immuni.2006.01.001
Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006) Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7(11):1151–1156. doi:10.1038/ni1391
Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupe P, Barillot E, Soumelis V (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9(6):650–657. doi:10.1038/ni.1613
Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ (2009) Identification of IL-17-producing FOXP3 + regulatory T cells in humans. Proc Natl Acad Sci USA 106(12):4793–4798. doi:10.1073/pnas.0900408106
Wang C, Wu L, Bulek K, Martin BN, Zepp JA, Kang Z, Liu C, Herjan T, Misra S, Carman JA, Gao J, Dongre A, Han S, Bunting KD, Ko JS, Xiao H, Kuchroo VK, Ouyang W, Li X (2013) The psoriasis-associated D10 N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. Nat Immunol 14(1):72–81. doi:10.1038/ni.2479
Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, Sleiman PM, Imielinski M, Glessner J, Hou C, Wilson DC, Walters T, Kim C, Frackelton EC, Lionetti P, Barabino A, Van Limbergen J, Guthery S, Denson L, Piccoli D, Li M, Dubinsky M, Silverberg M, Griffiths A, Grant SF, Satsangi J, Baldassano R, Hakonarson H (2009) Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn disease. Am J Hum Genet 84(3):399–405. doi:10.1016/j.ajhg.2009.01.026
Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206(7):1457–1464. doi:10.1084/jem.20090207
Wang L, Yi T, Zhang W, Pardoll DM, Yu H (2010) IL-17 enhances tumor development in carcinogen-induced skin cancer. Cancer Res 70(24):10112–10120. doi:10.1158/0008-5472.CAN-10-0775
Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, Schones DE, Peng W, Sun HW, Paul WE, O’Shea JJ, Zhao K (2009) Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4 + T cells. Immunity 30(1):155–167. doi:10.1016/j.immuni.2008.12.009
Wilson CB, Rowell E, Sekimata M (2009) Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9(2):91–105. doi:10.1038/nri2487
Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, de Waal Malefyt R (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957. doi:10.1038/ni1497
Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M, Vom Baur E, Witte K, Warszawska K, Philipp S, Johnson-Leger C, Volk HD, Sterry W, Sabat R (2009) IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med 87(5):523–536. doi:10.1007/s00109-009-0457-0
Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21(2):241–254. doi:10.1016/j.immuni.2004.07.007
Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36(5):1309–1323. doi:10.1002/eji.200535503
Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, Tomkinson KN, Fitz LJ, Wolfman NM, Collins M, Dunussi-Joannopoulos K, Chatterjee-Kishore M, Carreno BM (2008) The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. Journal of immunology 181(4):2799–2805
Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A, Kuchroo VK (2013) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496(7446):513–517. doi:10.1038/nature11984
Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15(9):1016–1022. doi:10.1038/nm.2015
Xiao S, Jin H, Korn T, Liu SM, Oukka M, Lim B, Kuchroo VK (2008) Retinoic acid increases Foxp3 + regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 181(4):2277–2284
Xie P, Stunz LL, Larison KD, Yang B, Bishop GA (2007) Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs. Immunity 27(2):253–267. doi:10.1016/j.immuni.2007.07.012
Xu L, Kitani A, Fuss I, Strober W (2007) Cutting edge: regulatory T cells induce CD4 + CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J immunol 178(11):6725–6729
Xu X, Weiss ID, HZ H, Singh SP, Wynn TA, Wilson MS, Farber JM (2014) Conventional NK Cells Can Produce IL-22 and Promote Host Defense in Klebsiella pneumoniae Pneumonia. J Immunol 192(4):1778–1786. doi:10.4049/jimmunol.1300039
Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Tsuno NH, Takahashi K, Yamamoto K (2007) IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J Immunol 179(10):7128–7136
Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454(7202):350–352. doi:10.1038/nature07021
Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C (2008) Regulation of inflammatory responses by IL-17F. J Exp Med 205(5):1063–1075. doi:10.1084/jem.20071978
Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, Feng XH, Jetten AM, Dong C (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1):44–56. doi:10.1016/j.immuni.2008.05.007
Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282(13):9358–9363. doi:10.1074/jbc.C600321200
Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28(1):29–39. doi:10.1016/j.immuni.2007.11.016
Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O’Shea JJ, Laurence A (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12(3):247–254. doi:10.1038/ni.1995
Yang Y, Xu J, Niu Y, Bromberg JS, Ding Y (2008) T-bet and eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17. Journal of immunology 181(12):8700–8710
Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X, Liao YH (2012) MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 7(10):e46082. doi:10.1371/journal.pone.0046082
Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI, Spriggs MK (1995) Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3(6):811–821
Yu Q, Sharma A, Ghosh A, Sen JM (2011) T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. Journal of immunology 186(7):3946–3952. doi:10.4049/jimmunol.1003497
Yu X, Rollins D, Ruhn KA, Stubblefield JJ, Green CB, Kashiwada M, Rothman PB, Takahashi JS, Hooper LV (2013) TH17 cell differentiation is regulated by the circadian clock. Science 342(6159):727–730. doi:10.1126/science.1243884
Zaph C, Du Y, Saenz SA, Nair MG, Perrigoue JG, Taylor BC, Troy AE, Kobuley DE, Kastelein RA, Cua DJ, Yu Y, Artis D (2008) Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med 205(10):2191–2198. doi:10.1084/jem.20080720
Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29(6):947–957. doi:10.1016/j.immuni.2008.11.003
Zepp JA, Liu C, Qian W, Wu L, Gulen MF, Kang Z, Li X (2012) Cutting Edge: TNF Receptor-Associated Factor 4 Restricts IL-17-Mediated Pathology and Signaling Processes. J Immunol 189(1):33–37. doi:10.4049/jimmunol.1200470
Zhang F, Meng G, Strober W (2008) Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol 9(11):1297–1306. doi:10.1038/ni.1663
Zhang GX, Gran B, Yu S, Li J, Siglienti I, Chen X, Kamoun M, Rostami A (2003) Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 170(4):2153–2160
Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, Wu C, Li SP, Zheng L (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50(5):980–989. doi:10.1016/j.jhep.2008.12.033
Zhang Y, Wang X, Zhong M, Zhang M, Suo Q, Lv K (2013) MicroRNA let-7a ameliorates con A-induced hepatitis by inhibiting IL-6-dependent Th17 cell differentiation. J Clin Immunol 33(3):630–639. doi:10.1007/s10875-012-9840-7
Zhang Z, Kyttaris VC, Tsokos GC (2009) The role of IL-23/IL-17 axis in lupus nephritis. J Immunol 183(5):3160–3169. doi:10.4049/jimmunol.0900385
Zhao A, Urban JF Jr, Sun R, Stiltz J, Morimoto M, Notari L, Madden KB, Yang Z, Grinchuk V, Ramalingam TR, Wynn TA, Shea-Donohue T (2010) Critical role of IL-25 in nematode infection-induced alterations in intestinal function. Journal of immunology 185(11):6921–6929. doi:10.4049/jimmunol.1000450
Zhao C, Dahlman-Wright K (2010) Liver X receptor in cholesterol metabolism. J Endocrinol 204(3):233–240. doi:10.1677/JOE-09-0271
Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445(7128):648–651. doi:10.1038/nature05505
Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14(3):282–289. doi:10.1038/nm1720
Zhong B, Liu X, Wang X, Chang SH, Wang A, Reynolds JM, Dong C (2012) Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. Nat Immunol 13(11):1110–1117. doi:10.1038/ni.2427
Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8(9):967–974. doi:10.1038/ni1488
Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453(7192):236–240. doi:10.1038/nature06878
Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33(2):229–240. doi:10.1016/j.immuni.2010.08.002
Zhou Y, Toh ML, Zrioual S, Miossec P (2007) IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. Cytokine 38(3):157–164. doi:10.1016/j.cyto.2007.06.002
Zhu J, Davidson TS, Wei G, Jankovic D, Cui K, Schones DE, Guo L, Zhao K, Shevach EM, Paul WE (2009) Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103 + inducible regulatory T cells. J Exp Med 206(2):329–341. doi:10.1084/jem.20081666
Zhu J, Guo L, Min B, Watson CJ, Hu-Li J, Young HA, Tsichlis PN, Paul WE (2002) Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16(5):733–744
Zhu S, Pan W, Qian Y (2013) MicroRNA in immunity and autoimmunity. J Mol Med 91(9):1039–1050. doi:10.1007/s00109-013-1043-z
Zhu S, Pan W, Shi P, Gao H, Zhao F, Song X, Liu Y, Zhao L, Li X, Shi Y, Qian Y (2010) Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling. J Exp Med 207(12):2647–2662. doi:10.1084/jem.20100703
Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, Liang D, He D, Wang H, Liu W, Shi Y, Harley JB, Shen N, Qian Y (2012) The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha. Nat Med 18(7):1077–1086. doi:10.1038/nm.2815
Zhu S, Qian Y (2012) IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci 122(11):487–511. doi:10.1042/CS20110496
Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J immunol 164(5):2832–2838
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Song, X., Gao, H., Qian, Y. (2014). Th17 Differentiation and Their Pro-inflammation Function. In: Sun, B. (eds) T Helper Cell Differentiation and Their Function. Advances in Experimental Medicine and Biology, vol 841. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9487-9_5
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