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Regulation of Interleukin-17 Production

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Regulation of Cytokine Gene Expression in Immunity and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 941))

Abstract

Innate immunity represents the first line of host defense against extracellular infections. Timely initiation of inflammatory responses to invading pathogens confers host the ability to prevent, restrict, and eliminate microorganisms and further trigger adaptive immunity to provide extended eradication of the pathogens as well as long-term protection of the host from recurrent infections. During this process, various types of cytokines are required for efficient immune responses, and interleukin 17 (IL-17) is one of them. The IL-17 family of cytokines bridges innate and adaptive immune responses and play an essential role in defining the Th17 cell lineage differentiation and function. Th17 cells have pivotal roles in protecting the host against extracellular pathogens as well as in promoting inflammatory pathology in autoimmune diseases. Strict regulation of the IL-17 family of cytokines at different levels ensures appropriate controls of their abilities to shape immune responses. This chapter provides the recent progress in the field of IL-17 studies for the understanding of the regulatory mechanisms in the expression and signaling of the IL-17 family cytokines. IL-17A (IL-17) is the most well-studied member in this family, while information on the other members is relatively sketchy. Thus, we mainly focus on the study of IL-17A.

The authors declare no conflict of interest.

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References

  1. Aggarwal S, Gurney AL. IL-17: prototype member of an emerging cytokine family. J Leukoc Biol. 2002;71:1–8.

    CAS  PubMed  Google Scholar 

  2. Akimzhanov AM, Yang XO, Dong C. Chromatin remodeling of interleukin-17 (IL-17)-IL-17F cytokine gene locus during inflammatory helper T cell differentiation. J Biol Chem. 2007;282:5969–72.

    Article  CAS  PubMed  Google Scholar 

  3. Algood HM, Allen SS, Washington MK, Peek Jr RM, Miller GG, Cover TL. Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection. J Immunol. 2009;183:5837–46.

    Article  PubMed  CAS  Google Scholar 

  4. An J, Golech S, Klaewsongkram J, Zhang Y, Subedi K, Huston GE, Wood 3rd WH, Wersto RP, Becker KG, Swain SL, et al. Kruppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation. FASEB J. 2011;25:3634–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anderson P. Post-transcriptional control of cytokine production. Nat Immunol. 2008;9:353–9.

    Article  CAS  PubMed  Google Scholar 

  6. Angkasekwinai P, Chang SH, Thapa M, Watarai H, Dong C. Regulation of IL-9 expression by IL-25 signaling. Nat Immunol. 2010;11:250–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Auger KR, Serunian LA, Soltoff SP, Libby P, Cantley LC. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell. 1989;57:167–75.

    Article  CAS  PubMed  Google Scholar 

  8. Becker S, Mundandhara S, Devlin RB, Madden M. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies. Toxicol Appl Pharmacol. 2005;207:269–75.

    Article  PubMed  CAS  Google Scholar 

  9. Bermejo DA, Jackson SW, Gorosito-Serran M, Acosta-Rodriguez EV, Amezcua-Vesely MC, Sather BD, Singh AK, Khim S, Mucci J, Liggitt D, et al. Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORgammat and Ahr that leads to IL-17 production by activated B cells. Nat Immunol. 2013;14:514–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Biswas PS, Gupta S, Chang E, Song L, Stirzaker RA, Liao JK, Bhagat G, Pernis AB. Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. J Clin Invest. 2010;120:3280–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Blonska M, Lin X. CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol Rev. 2009;228:199–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brereton CF, Sutton CE, Lalor SJ, Lavelle EC, Mills KH. Inhibition of ERK MAPK suppresses IL-23- and IL-1-driven IL-17 production and attenuates autoimmune disease. J Immunol. 2009;183:1715–23.

    Article  CAS  PubMed  Google Scholar 

  13. Bulek K, Liu C, Swaidani S, Wang L, Page RC, Gulen MF, Herjan T, Abbadi A, Qian W, Sun D, et al. The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol. 2011;12:844–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Caruso R, Stolfi C, Sarra M, Rizzo A, Fantini MC, Pallone F, MacDonald TT, Monteleone G. Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3. Blood. 2009;113:3512–9.

    Article  CAS  PubMed  Google Scholar 

  15. Chang SH, Park H, Dong C. Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem. 2006;281:35603–7.

    Article  CAS  PubMed  Google Scholar 

  16. Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C. Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity. 2011;35:611–21.

    Article  CAS  PubMed  Google Scholar 

  17. Chen J. The Src/PI3K/Akt pathway may play a key role in the production of IL-17 in obesity. J Leukoc Biol. 2010;87:355. author reply 357.

    Article  CAS  PubMed  Google Scholar 

  18. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB. IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity. 2008;29:899–911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen Z, Lin F, Gao Y, Li Z, Zhang J, Xing Y, Deng Z, Yao Z, Tsun A, Li B. FOXP3 and RORgammat: transcriptional regulation of Treg and Th17. Int Immunopharmacol. 2011;11:536–42.

    Article  CAS  PubMed  Google Scholar 

  20. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, Magorien JE, Blauvelt A, Kolls JK, Cheung AL, et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest. 2010;120:1762–73.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F, Agarwal A, Huang W, Parkurst CN, Muratet M, et al. A validated regulatory network for Th17 cell specification. Cell. 2012;151:289–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Claudio E, Sonder SU, Saret S, Carvalho G, Ramalingam TR, Wynn TA, Chariot A, Garcia-Perganeda A, Leonardi A, Paun A, et al. The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation. J Immunol. 2009;182:1617–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Crispin JC, Liossis SN, Kis-Toth K, Lieberman LA, Kyttaris VC, Juang YT, Tsokos GC. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med. 2010;16:47–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Crispin JC, Tsokos GC. Human TCR-alpha beta+ CD4–CD8- T cells can derive from CD8+ T cells and display an inflammatory effector phenotype. J Immunol. 2009;183:4675–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Crispin JC, Tsokos GC. IL-17 in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:943254.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89.

    Article  CAS  PubMed  Google Scholar 

  27. Curtis MM, Way SS. Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens. Immunology. 2009;126:177–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dolgachev V, Petersen BC, Budelsky AL, Berlin AA, Lukacs NW. Pulmonary IL-17E (IL-25) production and IL-17RB+ myeloid cell-derived Th2 cytokine production are dependent upon stem cell factor-induced responses during chronic allergic pulmonary disease. J Immunol. 2009;183:5705–15.

    Article  CAS  PubMed  Google Scholar 

  29. Dong C, Nurieva RI. Regulation of immune and autoimmune responses by ICOS. J Autoimmun. 2003;21:255–60.

    Article  PubMed  CAS  Google Scholar 

  30. Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, Fabien N, Cochat P, Pouteil-Noble C, Trolliet P, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10:778–85.

    Article  CAS  PubMed  Google Scholar 

  31. Eberl G, Littman DR. Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells. Science. 2004;305:248–51.

    Article  CAS  PubMed  Google Scholar 

  32. Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A, Shapiro AM. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes. 2009;58:1302–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Erbel C, Akhavanpoor M, Okuyucu D, Wangler S, Dietz A, Zhao L, Stellos K, Little KM, Lasitschka F, Doesch A, et al. IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis. J Immunol. 2014;193:4344–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Erdmann H, Rossnagel C, Bohme J, Iwakura Y, Jacobs T, Schaible UE, Holscher C. IL-17A promotes macrophage effector mechanisms against Trypanosoma cruzi by trapping parasites in the endolysosomal compartment. Immunobiology. 2013;218:910–23.

    Article  CAS  PubMed  Google Scholar 

  35. Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, McIlgorm A, Jolin HE, McKenzie AN. 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. 2006;203:1105–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Feng M, Wang Y, Chen K, Bian Z, Jinfang W, Gao Q. IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-kappaB signal pathway. PLoS One. 2014;9:e108502.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Furuta S, Jeng YM, Zhou L, Huang L, Kuhn I, Bissell MJ, Lee WH. IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells. Sci Transl Med. 2011;3:78ra31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9:556–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ganz T. Defensins and host defense. Science. 1999;286:420–1.

    Article  CAS  PubMed  Google Scholar 

  41. Garg AV, Ahmed M, Vallejo AN, Ma A, Gaffen SL. The deubiquitinase A20 mediates feedback inhibition of interleukin-17 receptor signaling. Sci Signal. 2013;6:ra44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Geremia A, Arancibia-Carcamo CV, Fleming MP, Rust N, Singh B, Mortensen NJ, Travis SP, Powrie F. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011;208:1127–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gislette T, Chen J. The possible role of IL-17 in obesity-associated cancer. Sci World J. 2010;10:2265–71.

    Article  CAS  Google Scholar 

  44. Gocke AR, Cravens PD, Ben LH, Hussain RZ, Northrop SC, Racke MK, Lovett-Racke AE. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J Immunol. 2007;178:1341–8.

    Article  CAS  PubMed  Google Scholar 

  45. Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted. Physiol Rev. 2007;87:69–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Groom J, Mackay F. B cells flying solo. Immunol Cell Biol. 2008;86:40–6.

    Article  CAS  PubMed  Google Scholar 

  47. Gu FM, Li QL, Gao Q, Jiang JH, Zhu K, Huang XY, Pan JF, Yan J, Hu JH, Wang Z, et al. IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma. Mol Cancer. 2011;10:150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Haas JD, Gonzalez FH, Schmitz S, Chennupati V, Fohse L, Kremmer E, Forster R, Prinz I. CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells. Eur J Immunol. 2009;39:3488–97.

    Article  CAS  PubMed  Google Scholar 

  49. Hamada S, Umemura M, Shiono T, Tanaka K, Yahagi A, Begum MD, Oshiro K, Okamoto Y, Watanabe H, Kawakami K, et al. IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver. J Immunol. 2008;181:3456–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Happel KI, Dubin PJ, Zheng M, Ghilardi N, Lockhart C, Quinton LJ, Odden AR, Shellito JE, Bagby GJ, Nelson S, et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med. 2005;202:761–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Happel KI, Zheng M, Young E, Quinton LJ, Lockhart E, Ramsay AJ, Shellito JE, Schurr JR, Bagby GJ, Nelson S, et al. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170:4432–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Harley IT, Stankiewicz TE, Giles DA, Softic S, Flick LM, Cappelletti M, Sheridan R, Xanthakos SA, Steinbrecher KA, Sartor RB, et al. IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology. 2014;59:1830–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hartupee J, Liu C, Novotny M, Li X, Hamilton T. IL-17 enhances chemokine gene expression through mRNA stabilization. J Immunol. 2007;179:4135–41.

    Article  CAS  PubMed  Google Scholar 

  54. Haudenschild D, Moseley T, Rose L, Reddi AH. Soluble and transmembrane isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer. J Biol Chem. 2002;277:4309–16.

    Article  CAS  PubMed  Google Scholar 

  55. Haudenschild DR, Curtiss SB, Moseley TA, Reddi AH. Generation of interleukin-17 receptor-like protein (IL-17RL) in prostate by alternative splicing of RNA. Prostate. 2006;66:1268–74.

    Article  CAS  PubMed  Google Scholar 

  56. Herjan T, Yao P, Qian W, Li X, Liu C, Bulek K, Sun D, Yang WP, Zhu J, He A, et al. HuR is required for IL-17-induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization. J Immunol. 2013;191:640–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Higgins SC, Jarnicki AG, Lavelle EC, Mills KH. TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol. 2006;177:7980–9.

    Article  CAS  PubMed  Google Scholar 

  58. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011;12:255–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Howe KL, Reardon C, Wang A, Nazli A, McKay DM. Transforming growth factor-beta regulation of epithelial tight junction proteins enhances barrier function and blocks enterohemorrhagic Escherichia coli O157:H7-induced increased permeability. Am J Pathol. 2005;167:1587–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, Yi J, Guentert T, Tousson A, Stanus AL, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.

    Article  CAS  PubMed  Google Scholar 

  61. Hu R, O’Connell RM. MiR-23b is a safeguard against autoimmunity. Nat Med. 2012;18:1009–10.

    Article  CAS  PubMed  Google Scholar 

  62. Huang F, Kao CY, Wachi S, Thai P, Ryu J, Wu R. Requirement for both JAK-mediated PI3K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol. 2007;179:6504–13.

    Article  CAS  PubMed  Google Scholar 

  63. Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, Melendez AJ, McInnes IB. Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol. 2010;184:3336–40.

    Article  CAS  PubMed  Google Scholar 

  64. Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, Menon S, Seymour B, Jackson C, Kung TT, et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol. 2002;169:443–53.

    Article  CAS  PubMed  Google Scholar 

  65. Hwang ES. Transcriptional regulation of T helper 17 cell differentiation. Yonsei Med J. 2010;51:484–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, et al. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J. 2001;20:5332–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T. Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem. 2008;283:17003–8.

    Article  CAS  PubMed  Google Scholar 

  68. Ikeda K, Nakajima H, Suzuki K, Kagami S, Hirose K, Suto A, Saito Y, Iwamoto I. Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation. Blood. 2003;101:3594–6.

    Article  CAS  PubMed  Google Scholar 

  69. Isailovic N, Daigo K, Mantovani A, Selmi C. Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun. 2015;60:1–11.

    Article  CAS  PubMed  Google Scholar 

  70. Ise W, Kohyama M, Schraml BU, Zhang T, Schwer B, Basu U, Alt FW, Tang J, Oltz EM, Murphy TL, et al. The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat Immunol. 2011;12:536–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009;30:108–19.

    Article  CAS  PubMed  Google Scholar 

  72. Ito R, Kita M, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Iwakura Y, Okanoue T, et al. Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. Biochem Biophys Res Commun. 2008;377:12–6.

    Article  CAS  PubMed  Google Scholar 

  73. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.

    Article  CAS  PubMed  Google Scholar 

  74. Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity. 2011;34:149–62.

    Article  CAS  PubMed  Google Scholar 

  75. Jain R, Tartar DM, Gregg RK, Divekar RD, Bell JJ, Lee HH, Yu P, Ellis JS, Hoeman CM, Franklin CL, et al. Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med. 2008;205:207–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jetten AM, Kurebayashi S, Ueda E. The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes. Prog Nucleic Acid Res Mol Biol. 2001;69:205–47.

    Article  CAS  PubMed  Google Scholar 

  77. Jin W, Dong C. IL-17 cytokines in immunity and inflammation. Emerg Microbes Infect. 2013;2:e60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Johansen C, Riis JL, Gedebjerg A, Kragballe K, Iversen L. Tumor necrosis factor alpha-mediated induction of interleukin 17C in human keratinocytes is controlled by nuclear factor kappaB. J Biol Chem. 2011;286:25487–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol. 2009;160:319–24.

    Article  CAS  PubMed  Google Scholar 

  80. Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, Chen CS, Fu W, Gudjonsson JE, McCormick TS, et al. Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol. 2013;190:2252–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jones CE, Chan K. Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells. Am J Respir Cell Mol Biol. 2002;26:748–53.

    Article  CAS  PubMed  Google Scholar 

  82. Jovcic G, Bugarski D, Krstic A, Vlaski M, Petakov M, Mojsilovic S, Stojanovic N, Milenkovic P. The effect of interleukin-17 on hematopoietic cells and cytokine release in mouse spleen. Physiol Res/Acad Sci Bohemoslovaca. 2007;56:331–9.

    CAS  Google Scholar 

  83. Kao CY, Chen Y, Thai P, Wachi S, Huang F, Kim C, Harper RW, Wu R. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol. 2004;173:3482–91.

    Article  CAS  PubMed  Google Scholar 

  84. Kappel LW, Goldberg GL, King CG, Suh DY, Smith OM, Ligh C, Holland AM, Grubin J, Mark NM, Liu C, et al. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood. 2009;113:945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM, Blumenschein WM, McClanahan T, Brombacher F, Hurst SD, et al. IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med. 2007;204:161–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, Hucke S, Alferink J, Nowak N, Beyer M, Mayer G, et al. The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med. 2009;206:2079–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kobayashi S, Hara A, Isagawa T, Manabe I, Takeda K, MaruYama T. The nuclear IkappaB family protein IkappaBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model. PLoS One. 2014;9:e110838.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–76.

    Article  CAS  PubMed  Google Scholar 

  89. Krstic A, Ilic V, Mojsilovic S, Jovcic G, Milenkovic P, Bugarski D. p38 MAPK signaling mediates IL-17-induced nitric oxide synthase expression in bone marrow cells. Growth Factors. 2009;27:79–90.

    Article  CAS  PubMed  Google Scholar 

  90. Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL, et al. Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol. 2007;179:5462–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Laan M, Lotvall J, Chung KF, Linden A. IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. Br J Pharmacol. 2001;133:200–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Larochelle C, Alvarez JI, Prat A. How do immune cells overcome the blood-brain barrier in multiple sclerosis? FEBS Lett. 2011;585:3770–80.

    Article  CAS  PubMed  Google Scholar 

  94. le Rolle AF, Chiu TK, Fara M, Shia J, Zeng Z, Weiser MR, Paty PB, Chiu VK. The prognostic significance of CXCL1 hypersecretion by human colorectal cancer epithelia and myofibroblasts. J Transl Med. 2015;13:199.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Lebson L, Gocke A, Rosenzweig J, Alder J, Civin C, Calabresi PA, Whartenby KA. Cutting edge: the transcription factor Kruppel-like factor 4 regulates the differentiation of Th17 cells independently of RORgammat. J Immunol. 2010;185:7161–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lee J, Ho WH, Maruoka M, Corpuz RT, Baldwin DT, Foster JS, Goddard AD, Yansura DG, Vandlen RL, Wood WI, et al. IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. J Biol Chem. 2001;276:1660–4.

    Article  CAS  PubMed  Google Scholar 

  97. LeGrand A, Fermor B, Fink C, Pisetsky DS, Weinberg JB, Vail TP, Guilak F. Interleukin-1, tumor necrosis factor alpha, and interleukin-17 synergistically up-regulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci. Arthritis Rheum. 2001;44:2078–83.

    Article  CAS  PubMed  Google Scholar 

  98. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–89.

    Article  CAS  PubMed  Google Scholar 

  99. Li B, Reynolds JM, Stout RD, Bernlohr DA, Suttles J. Regulation of Th17 differentiation by epidermal fatty acid-binding protein. J Immunol. 2009;182:7625–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, Dowd P, Gurney AL, Wood WI. Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci U S A. 2000;97:773–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Li L, Patsoukis N, Petkova V, Boussiotis VA. Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells. PLoS One. 2012;7:e45115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006;203:2271–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Liao JJ, Huang MC, Goetzl EJ. Cutting edge: alternative signaling of Th17 cell development by sphingosine 1-phosphate. J Immunol. 2007;178:5425–8.

    Article  CAS  PubMed  Google Scholar 

  104. Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnolzer M, et al. SIRT1 deacetylates RORgammat and enhances Th17 cell generation. J Exp Med. 2015;212:973.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Lindemann MJ, Hu Z, Benczik M, Liu KD, Gaffen SL. Differential regulation of the IL-17 receptor by gammac cytokines: inhibitory signaling by the phosphatidylinositol 3-kinase pathway. J Biol Chem. 2008;283:14100–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Liu HP, Cao AT, Feng T, Li Q, Zhang W, Yao S, Dann SM, Elson CO, Cong Y. TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1 expression. Eur J Immunol. 2015;45:1010–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lockhart E, Green AM, Flynn JL. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol. 2006;177:4662–9.

    Article  CAS  PubMed  Google Scholar 

  108. Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, et al. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog. 2008;4:e1000159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Lubberts E, Joosten LA, van de Loo FA, Schwarzenberger P, Kolls J, van den Berg WB. Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm Res. 2002;51:102–4.

    Article  CAS  PubMed  Google Scholar 

  110. Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB. 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. 2004;50:650–9.

    Article  CAS  PubMed  Google Scholar 

  111. Lubberts E, van den Berg WB. Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. Adv Exp Med Biol. 2003;520:194–202.

    Article  CAS  PubMed  Google Scholar 

  112. Maezawa Y, Nakajima H, Suzuki K, Tamachi T, Ikeda K, Inoue J, Saito Y, Iwamoto I. Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling. J Immunol. 2006;176:1013–8.

    Article  CAS  PubMed  Google Scholar 

  113. Mai J, Virtue A, Maley E, Tran T, Yin Y, Meng S, Pansuria M, Jiang X, Wang H, Yang XF. MicroRNAs and other mechanisms regulate interleukin-17 cytokines and receptors. Front Biosci. 2012;4:1478–95.

    Article  Google Scholar 

  114. Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M. Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity. 2009;31:321–30.

    Article  CAS  PubMed  Google Scholar 

  115. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8:1390–7.

    Article  CAS  PubMed  Google Scholar 

  116. Meeks KD, Sieve AN, Kolls JK, Ghilardi N, Berg RE. IL-23 is required for protection against systemic infection with Listeria monocytogenes. J Immunol. 2009;183:8026–34.

    Article  CAS  PubMed  Google Scholar 

  117. Miao T, Raymond M, Bhullar P, Ghaffari E, Symonds AL, Meier UC, Giovannoni G, Li S, Wang P. Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf. J Immunol. 2013;190:58–65.

    Article  CAS  PubMed  Google Scholar 

  118. Michel ML, Keller AC, Paget C, Fujio M, Trottein F, Savage PB, Wong CH, Schneider E, Dy M, Leite-de-Moraes MC. Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med. 2007;204:995–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008;452:773–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Moran EM, Mullan R, McCormick J, Connolly M, Sullivan O, Fitzgerald O, Bresnihan B, Veale DJ, Fearon U. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies. Arthritis Res Ther. 2009;11:R113.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Moreira-Teixeira L, Resende M, Coffre M, Devergne O, Herbeuval JP, Hermine O, Schneider E, Rogge L, Ruemmele FM, Dy M, et al. Proinflammatory environment dictates the IL-17-producing capacity of human invariant NKT cells. J Immunol. 2011;186:5758–65.

    Article  CAS  PubMed  Google Scholar 

  122. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.

    CAS  PubMed  Google Scholar 

  123. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–7.

    Article  CAS  PubMed  Google Scholar 

  124. Nascimento MS, Carregaro V, Lima-Junior DS, Costa DL, Ryffel B, Duthie MS, de Jesus A, de Almeida RP, da Silva JS. Interleukin 17A acts synergistically with interferon gamma to promote protection against Leishmania infantum infection. J Infect Dis. 2015;211:1015–26.

    Article  PubMed  Google Scholar 

  125. Nigam P, Kwa S, Velu V, Amara RR. Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection. J Immunol. 2011;186:745–53.

    Article  CAS  PubMed  Google Scholar 

  126. Novatchkova M, Leibbrandt A, Werzowa J, Neubuser A, Eisenhaber F. The STIR-domain superfamily in signal transduction, development and immunity. Trends Biochem Sci. 2003;28:226–9.

    Article  CAS  PubMed  Google Scholar 

  127. Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y. Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol. 2004;110:55–62.

    Article  CAS  PubMed  Google Scholar 

  128. Ogura H, Murakami M, Okuyama Y, Tsuruoka M, Kitabayashi C, Kanamoto M, Nishihara M, Iwakura Y, Hirano T. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity. 2008;29:628–36.

    Article  CAS  PubMed  Google Scholar 

  129. Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010;129:311–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ouyang X, Zhang R, Yang J, Li Q, Qin L, Zhu C, Liu J, Ning H, Shin MS, Gupta M, et al. Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. Nat Commun. 2011;2:314.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Ozaki K, Leonard WJ. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem. 2002;277:29355–8.

    Article  CAS  PubMed  Google Scholar 

  132. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Passos ST, Silver JS, O’Hara AC, Sehy D, Stumhofer JS, Hunter CA. IL-6 promotes NK cell production of IL-17 during toxoplasmosis. J Immunol. 2010;184:1776–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Pham D, Sehra S, Sun X, Kaplan MH. The transcription factor Etv5 controls TH17 cell development and allergic airway inflammation. J Allergy Clin Immunol. 2014;134:204–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Qi CF, Li Z, Raffeld M, Wang H, Kovalchuk AL, Morse 3rd HC. Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments. Immunol Res. 2009;45:62–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J, et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol. 2007;8:247–56.

    Article  CAS  PubMed  Google Scholar 

  137. Rachitskaya AV, Hansen AM, Horai R, Li Z, Villasmil R, Luger D, Nussenblatt RB, Caspi RR. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol. 2008;180:5167–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, Godinez I, Sankaran S, Paixao TA, Gordon MA, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14:421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J, Hackney J, Kim J, Zhou M, Lai J, et al. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol. 2011;12:1159–66.

    Article  CAS  PubMed  Google Scholar 

  140. Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, Agurell E, Grafstrom AK. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J Biol Chem. 1987;262:15422–7.

    CAS  PubMed  Google Scholar 

  141. Reynolds JM, Martinez GJ, Nallaparaju KC, Chang SH, Wang YH, Dong C. Cutting edge: regulation of intestinal inflammation and barrier function by IL-17C. J Immunol. 2012;189:4226–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Reynolds JM, Pappu BP, Peng J, Martinez GJ, Zhang Y, Chung Y, Ma L, Yang XO, Nurieva RI, Tian Q, et al. Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity. 2010;32:692–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, Girardi M, Borst J, Hayday AC, Pennington DJ, et al. CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets. Nat Immunol. 2009;10:427–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Rickel EA, Siegel LA, Yoon BR, Rottman JB, Kugler DG, Swart DA, Anders PM, Tocker JE, Comeau MR, Budelsky AL. Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J Immunol. 2008;181:4299–310.

    Article  CAS  PubMed  Google Scholar 

  145. Rong Z, Cheng L, Ren Y, Li Z, Li Y, Li X, Li H, Fu XY, Chang Z. Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. Cell Signal. 2007;19:1514–20.

    Article  CAS  PubMed  Google Scholar 

  146. Rouvier E, Luciani MF, Mattei MG, Denizot F, Golstein P. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993;150:5445–56.

    CAS  PubMed  Google Scholar 

  147. Ruan Q, Kameswaran V, Zhang Y, Zheng S, Sun J, Wang J, DeVirgiliis J, Liou HC, Beg AA, Chen YH. The Th17 immune response is controlled by the Rel-RORgamma-RORgamma T transcriptional axis. J Exp Med. 2011;208:2321–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Ruddy MJ, Wong GC, Liu XK, Yamamoto H, Kasayama S, Kirkwood KL, Gaffen SL. Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members. J Biol Chem. 2004;279:2559–67.

    Article  CAS  PubMed  Google Scholar 

  149. Rudner XL, Happel KI, Young EA, Shellito JE. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect Immun. 2007;75:3055–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ryzhakov G, Blazek K, Lai CC, Udalova IA. IL-17 receptor adaptor protein Act1/CIKS plays an evolutionarily conserved role in antiviral signaling. J Immunol. 2012;189:4852–8.

    Article  CAS  PubMed  Google Scholar 

  151. Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, et al. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity. 2010;32:681–91.

    Article  CAS  PubMed  Google Scholar 

  152. Sakellariou GT, Anastasilakis AD, Bisbinas I, Oikonomou D, Gerou S, Polyzos SA, Sayegh FE. Circulating periostin levels in patients with AS: association with clinical and radiographic variables, inflammatory markers and molecules involved in bone formation. Rheumatology. 2015;54:908–14.

    Article  PubMed  Google Scholar 

  153. Saleh A, Shan L, Halayko AJ, Kung S, Gounni AS. Critical role for STAT3 in IL-17A-mediated CCL11 expression in human airway smooth muscle cells. J Immunol. 2009;182:3357–65.

    Article  CAS  PubMed  Google Scholar 

  154. Sawa S, Lochner M, Satoh-Takayama N, Dulauroy S, Berard M, Kleinschek M, Cua D, Di Santo JP, Eberl G. RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol. 2011;12:320–6.

    Article  CAS  PubMed  Google Scholar 

  155. Schecter A, Birnbaum L, Ryan JJ, Constable JD. Dioxins: an overview. Environ Res. 2006;101:419–28.

    Article  CAS  PubMed  Google Scholar 

  156. Serody JS, Hill GR. The IL-17 differentiation pathway and its role in transplant outcome. Biol Blood Marrow Transplant. 2012;18:S56–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Shahrara S, Pickens SR, Mandelin 2nd AM, Karpus WJ, Huang Q, Kolls JK, Pope RM. IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte chemoattractant protein-1 induction. J Immunol. 2010;184:4479–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Shen F, Gaffen SL. Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine. 2008;41:92–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Shen F, Hu Z, Goswami J, Gaffen SL. Identification of common transcriptional regulatory elements in interleukin-17 target genes. J Biol Chem. 2006;281:24138–48.

    Article  CAS  PubMed  Google Scholar 

  160. Shen F, Li N, Gade P, Kalvakolanu DV, Weibley T, Doble B, Woodgett JR, Wood TD, Gaffen SL. IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain. Sci Signal. 2009;2:ra8.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Shen F, Ruddy MJ, Plamondon P, Gaffen SL. Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-alpha-induced genes in bone cells. J Leukoc Biol. 2005;77:388–99.

    Article  CAS  PubMed  Google Scholar 

  162. Shi P, Zhu S, Lin Y, Liu Y, Liu Y, Chen Z, Shi Y, Qian Y. Persistent stimulation with interleukin-17 desensitizes cells through SCFbeta-TrCP-mediated degradation of Act1. Sci Signal. 2011;4:ra73.

    Article  PubMed  CAS  Google Scholar 

  163. Shi Y, Ullrich SJ, Zhang J, Connolly K, Grzegorzewski KJ, Barber MC, Wang W, Wathen K, Hodge V, Fisher CL, et al. A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity. J Biol Chem. 2000;275:19167–76.

    Article  CAS  PubMed  Google Scholar 

  164. Shibata K, Yamada H, Hara H, Kishihara K, Yoshikai Y. Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J Immunol. 2007;178:4466–72.

    Article  CAS  PubMed  Google Scholar 

  165. Song X, Zhu S, Shi P, Liu Y, Shi Y, Levin SD, Qian Y. IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nat Immunol. 2011;12:1151–8.

    Article  CAS  PubMed  Google Scholar 

  166. Souwer Y, Szegedi K, Kapsenberg ML, de Jong EC. IL-17 and IL-22 in atopic allergic disease. Curr Opin Immunol. 2010;22:821–6.

    Article  CAS  PubMed  Google Scholar 

  167. Starnes T, Broxmeyer HE, Robertson MJ, Hromas R. Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J Immunol. 2002;169:642–6.

    Article  CAS  PubMed  Google Scholar 

  168. Stock P, Lombardi V, Kohlrautz V, Akbari O. Induction of airway hyperreactivity by IL-25 is dependent on a subset of invariant NKT cells expressing IL-17RB. J Immunol. 2009;182:5116–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, Fujiyama Y, Andoh A. The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol. 2010;160:386–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Sun D, Novotny M, Bulek K, Liu C, Li X, Hamilton T. 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. 2011;12:853–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, Littman DR. Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science. 2000;288:2369–73.

    Article  CAS  PubMed  Google Scholar 

  172. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31:331–41.

    Article  CAS  PubMed  Google Scholar 

  173. Swaidani S, Bulek K, Kang Z, Gulen MF, Liu C, Yin W, Abbadi A, Aronica M, Li X. T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic airway inflammation. J Immunol. 2011;187:3155–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Swaidani S, Bulek K, Kang Z, Liu C, Lu Y, Yin W, Aronica M, Li X. The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation. J Immunol. 2009;182:1631–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Terashima A, Watarai H, Inoue S, Sekine E, Nakagawa R, Hase K, Iwamura C, Nakajima H, Nakayama T, Taniguchi M. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. J Exp Med. 2008;205:2727–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 2006;177:36–9.

    Article  CAS  PubMed  Google Scholar 

  177. Trajkovic V, Stosic-Grujicic S, Samardzic T, Markovic M, Miljkovic D, Ramic Z, Mostarica Stojkovic M. Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes. J Neuroimmunol. 2001;119:183–91.

    Article  CAS  PubMed  Google Scholar 

  178. Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, Suda T, Sudo K, Nakae S, Iwakura Y, et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol. 2007;178:3786–96.

    Article  CAS  PubMed  Google Scholar 

  179. Wang X, Zhang Y, Yang XO, Nurieva RI, Chang SH, Ojeda SS, Kang HS, Schluns KS, Gui J, Jetten AM, et al. Transcription of Il17 and Il17f is controlled by conserved noncoding sequence 2. Immunity. 2012;36:23–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007;204:1837–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008;127:385–93.

    Article  CAS  PubMed  Google Scholar 

  182. Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, Tomkinson KN, Fitz LJ, Wolfman NM, Collins M, et al. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol. 2008;181:2799–805.

    Article  CAS  PubMed  Google Scholar 

  183. Wright JF, Guo Y, Quazi A, Luxenberg DP, Bennett F, Ross JF, Qiu Y, Whitters MJ, Tomkinson KN, Dunussi-Joannopoulos K, et al. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem. 2007;282:13447–55.

    Article  CAS  PubMed  Google Scholar 

  184. Xu S, Han Y, Xu X, Bao Y, Zhang M, Cao X. IL-17A-producing gammadeltaT cells promote CTL responses against Listeria monocytogenes infection by enhancing dendritic cell cross-presentation. J Immunol. 2010;185:5879–87.

    Article  CAS  PubMed  Google Scholar 

  185. Yagi Y, Andoh A, Inatomi O, Tsujikawa T, Fujiyama Y. Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts. J Gastroenterol. 2007;42:746–53.

    Article  CAS  PubMed  Google Scholar 

  186. Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Tsuno NH, Takahashi K, Yamamoto K. IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J Immunol. 2007;179:7128–36.

    Article  CAS  PubMed  Google Scholar 

  187. Yang B, Kang H, Fung A, Zhao H, Wang T, Ma D. The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis. Mediators Inflamm. 2014;2014:623759.

    PubMed  PubMed Central  Google Scholar 

  188. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999;286:525–8.

    Article  CAS  PubMed  Google Scholar 

  189. Yang TT, Chow CW. Transcription cooperation by NFAT.C/EBP composite enhancer complex. J Biol Chem. 2003;278:15874–85.

    Article  CAS  PubMed  Google Scholar 

  190. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, et al. Regulation of inflammatory responses by IL-17F. J Exp Med. 2008;205:1063–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008;28:29–39.

    Article  CAS  PubMed  Google Scholar 

  192. Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI, Spriggs MK. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity. 1995;3:811–21.

    Article  CAS  PubMed  Google Scholar 

  193. Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, Armitage RJ. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995;155:5483–6.

    CAS  PubMed  Google Scholar 

  194. Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001;194:519–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Yeste A, Mascanfroni ID, Nadeau M, Burns EJ, Tukpah AM, Santiago A, Wu C, Patel B, Kumar D, Quintana FJ. IL-21 induces IL-22 production in CD4+ T cells. Nat Commun. 2014;5:3753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Zepp JA, Liu C, Qian W, Wu L, Gulen MF, Kang Z, Li X. Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes. J Immunol. 2012;189:33–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Zhang B, Liu C, Qian W, Han Y, Li X, Deng J. Crystal structure of IL-17 receptor B SEFIR domain. J Immunol. 2013;190:2320–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Zhang F, Meng G, Strober W. Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol. 2008;9:1297–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Zhang Z, Kyttaris VC, Tsokos GC. The role of IL-23/IL-17 axis in lupus nephritis. J Immunol. 2009;183:3160–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Zhao A, Urban Jr JF, Sun R, Stiltz J, Morimoto M, Notari L, Madden KB, Yang Z, Grinchuk V, Ramalingam TR, et al. Critical role of IL-25 in nematode infection-induced alterations in intestinal function. J Immunol. 2010;185:6921–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Zhong B, Liu X, Wang X, Chang SH, Liu X, Wang A, Reynolds JM, Dong C. Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. Nat Immunol. 2012;13:1110–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Zhou L, Littman DR. Transcriptional regulatory networks in Th17 cell differentiation. Curr Opin Immunol. 2009;21:146–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  203. Zhu S, Pan W, Shi P, Gao H, Zhao F, Song X, Liu Y, Zhao L, Li X, Shi Y, et al. Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling. J Exp Med. 2010;207:2647–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, Liang D, He D, Wang H, Liu W, et al. The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha. Nat Med. 2012;18:1077–86.

    Article  CAS  PubMed  Google Scholar 

  205. Zizzo G, Cohen PL. IL-17 stimulates differentiation of human anti-inflammatory macrophages and phagocytosis of apoptotic neutrophils in response to IL-10 and glucocorticoids. J Immunol. 2013;190:5237–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Dong, W., Ma, X. (2016). Regulation of Interleukin-17 Production. In: Ma, X. (eds) Regulation of Cytokine Gene Expression in Immunity and Diseases. Advances in Experimental Medicine and Biology, vol 941. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0921-5_7

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