IL-22 and IL-17: Common and different properties

  • Robert Sabat
  • Katrin Witte
  • Kerstin Wolk
Part of the Progress in Inflammation Research book series (PIR)


Many studies over the last few years have shown that a subpopulation of T helper cells called Th17 cells play a major role in both the defense against certain microbes and the development and maintenance of chronic inflammatory diseases. IL-22, IL-17A, and IL-17F may be the most important effector mediators of this novel cell population. This chapter illuminates the common and differing properties of IL-22, IL-17A, and IL-17F with respect to their genes, protein structure, cellular sources, receptors, target cells, and biological effects. Surprisingly, with the exception of a few similarities (in part identical producing cell types and responding cells), most basic aspects of IL-22 and IL-17A/IL-17F are different.


Th17 Cell Experimental Autoimmune Encephalomyelitis Receptor Chain Inflame Intestine Colonic Subepithelial Myofibroblasts 


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  1. 1.
    Volk H, Asadullah K, Gallagher G, Sabat R, Grutz G (2001) IL-10 and its homologs: Important immune mediators and emerging immunotherapeutic targets. Trends Immunol 22: 414–417PubMedCrossRefGoogle Scholar
  2. 2.
    Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H (2004) The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol 76: 314–321PubMedCrossRefGoogle Scholar
  3. 3.
    Langer JA, Cutrone EC, Kotenko S (2004) The class II cytokine receptor (CRF2) family: Overview and patterns of receptor-ligand interactions. Cytokine Growth Factor Rev 15: 33–48PubMedCrossRefGoogle Scholar
  4. 4.
    Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22: 929–979PubMedCrossRefGoogle Scholar
  5. 5.
    Sabat R, Wallace E, Endesfelder S, Wolk K (2007) IL-19 and IL-20: Two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 11: 601–612PubMedCrossRefGoogle Scholar
  6. 6.
    Wolk K, Sabat R (2006) Interleukin-22: A novel T-and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine Growth Factor Rev 17: 367–380PubMedCrossRefGoogle Scholar
  7. 7.
    Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21: 467–476PubMedCrossRefGoogle Scholar
  8. 8.
    Moseley TA, Haudenschild DR, Rose L, Reddi AH (2003) Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 14: 155–174PubMedCrossRefGoogle Scholar
  9. 9.
    Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL (2000) Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem 275: 31335–31339PubMedCrossRefGoogle Scholar
  10. 10.
    Nagem RA, Colau D, Dumoutier L, Renauld JC, Ogata C, Polikarpov I (2002) Crystal structure of recombinant human interleukin-22. Structure (Camb) 10: 1051–1062CrossRefGoogle Scholar
  11. 11.
    Xu T, Logsdon NJ, Walter MR (2005) Structure of insect-cell-derived IL-22. Acta Crystallogr D Biol Crystallogr 61: 942–950PubMedCrossRefGoogle Scholar
  12. 12.
    Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR (2002) Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J Interferon Cytokine Res 22: 1099–1112PubMedCrossRefGoogle Scholar
  13. 13.
    Walter MR, Nagabhushan TL (1995) Crystal structure of interleukin 10 reveals an interferon gamma-like fold. Biochemistry 34: 12118–12125PubMedCrossRefGoogle Scholar
  14. 14.
    Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (1995) Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure 3: 591–601PubMedCrossRefGoogle Scholar
  15. 15.
    Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H, Donnelly RP, Pestka S (2001) Identification of the functional interleukin-22 (IL-22) receptor complex: The IL-10R2 chain (IL-10Rbeta) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J Biol Chem 276: 2725–2732PubMedCrossRefGoogle Scholar
  16. 16.
    Logsdon NJ, Jones BC, Allman JC, Izotova L, Schwartz B, Pestka S, Walter MR (2004) The IL-10R2 binding hot spot on IL-22 is located on the N-terminal helix and is dependent on N-linked glycosylation. J Mol Biol 342: 503–514PubMedCrossRefGoogle Scholar
  17. 17.
    Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF et al (2001) IL-17s adopt a cystine knot fold: Structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J 20: 5332–5341PubMedCrossRefGoogle Scholar
  18. 18.
    McDonald NQ, Hendrickson WA (1993) A structural superfamily of growth factors containing a cystine knot motif. Cell 73: 421–424PubMedCrossRefGoogle Scholar
  19. 19.
    Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28: 454–467PubMedCrossRefGoogle Scholar
  20. 20.
    Dumoutier L, Louahed J, Renauld JC (2000) Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol 164: 1814–1819PubMedGoogle Scholar
  21. 21.
    Wolk K, Kunz S, Asadullah K, Sabat R (2002) Cutting edge: Immune cells as sources and targets of the IL-10 family members? J Immunol 168: 5397–5402PubMedGoogle Scholar
  22. 22.
    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: 1309–1323PubMedCrossRefGoogle Scholar
  23. 23.
    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: 1123–1132PubMedCrossRefGoogle Scholar
  24. 24.
    Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q et al (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6: 1133–1141PubMedCrossRefGoogle Scholar
  25. 25.
    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: 650–657PubMedCrossRefGoogle Scholar
  26. 26.
    Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C (2006) Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 16: 902–907PubMedCrossRefGoogle Scholar
  27. 27.
    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: 2271–2279PubMedCrossRefGoogle Scholar
  28. 28.
    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: 648–651PubMedCrossRefGoogle Scholar
  29. 29.
    Wolk K, Witte K, Witte E, Proesch S, Schulze-Tanzil G, Nasilowska K, Thilo J, Asadullah K, Sterry W, Volk HD et al (2008) Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes. J Leukoc Biol 83: 1181–1193PubMedCrossRefGoogle Scholar
  30. 30.
    Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21: 241–254PubMedCrossRefGoogle Scholar
  31. 31.
    Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, deSauvage FJ et al (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14: 282–289PubMedCrossRefGoogle Scholar
  32. 32.
    Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, Hassan HY, Wilkinson RJ, Walzl G, Gelderbloem SJ et al (2008) Distinct, specific IL-17-and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180: 1962–1970PubMedGoogle Scholar
  33. 33.
    Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A et al (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129: 969–984PubMedCrossRefGoogle Scholar
  34. 34.
    Wolk K, Witte E, Hoffmann U, Doecke WD, Endesfelder S, Asadullah K, Sterry W, Volk HD, Wittig BM, Sabat R (2007) IL-22 induces lipopolysaccharide-binding protein in hepatocytes: A potential systemic role of IL-22 in Crohn’s disease. J Immunol 178: 5973–5981PubMedGoogle Scholar
  35. 35.
    Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, Nojima Y (2005) Expression of interleukin-22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine. Arthritis Rheum 52: 1037–1046PubMedCrossRefGoogle Scholar
  36. 36.
    Whittington HA, Armstrong L, Uppington KM, Millar AB (2004) Interleukin-22: A potential immunomodulatory molecule in the lung. Am J Respir Cell Mol Biol 31: 220–226PubMedCrossRefGoogle Scholar
  37. 37.
    Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K et al (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14: 275–281PubMedCrossRefGoogle Scholar
  38. 38.
    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: 8098–8104PubMedGoogle Scholar
  39. 39.
    Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, Senices M, Gill D, Dunussi-Joannopoulos K, Collins M et al (2008) IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118: 597–607PubMedGoogle Scholar
  40. 40.
    Radaeva S, Sun R, Pan HN, Hong F, Gao B (2004) Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39: 1332–1342PubMedCrossRefGoogle Scholar
  41. 41.
    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: 534–544PubMedGoogle Scholar
  42. 42.
    Weber GF, Schlautkotter S, Kaiser-Moore S, Altmayr F, Holzmann B, Weighardt H (2007) Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. Infect Immun 75: 1690–1697PubMedCrossRefGoogle Scholar
  43. 43.
    Wolk K, Witte E, Reineke U, Witte K, Friedrich M, Sterry W, Asadullah K, Volk HD, Sabat R (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes Immun 6: 8–18PubMedCrossRefGoogle Scholar
  44. 44.
    Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA (2007) Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27: 647–659PubMedCrossRefGoogle Scholar
  45. 45.
    Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8: 639–646PubMedCrossRefGoogle Scholar
  46. 46.
    Bettelli E, Korn T, Kuchroo VK (2007) Th17: The third member of the effector T cell trilogy. Curr Opin Immunol 19: 652–657PubMedCrossRefGoogle Scholar
  47. 47.
    Dumoutier L, Van Roost E, Colau D, Renauld JC (2000) Human interleukin-10-related T cell-derived inducible factor: Molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc Natl Acad Sci USA 97: 10144–10149PubMedCrossRefGoogle Scholar
  48. 48.
    Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S (1997) Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J 16: 5894–5903PubMedCrossRefGoogle Scholar
  49. 49.
    Li J, Tomkinson KN, Tan XY, Wu P, Yan G, Spaulding V, Deng B, Annis-Freeman B, Heveron K, Zollner R et al (2004) Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2. Int Immunopharmacol 4: 693–708PubMedCrossRefGoogle Scholar
  50. 50.
    Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL et al (2007) Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol 179: 5462–5473PubMedGoogle Scholar
  51. 51.
    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: 36–39PubMedGoogle Scholar
  52. 52.
    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: 811–821PubMedCrossRefGoogle Scholar
  53. 53.
    Haudenschild D, Moseley T, Rose L, Reddi AH (2002) Soluble and transmembrane isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer. J Biol Chem 277: 4309–4316PubMedCrossRefGoogle Scholar
  54. 54.
    Kramer JM, Hanel W, Shen F, Isik N, Malone JP, Maitra A, Sigurdson W, Swart D, Tocker J, Jin T et al (2007) Cutting edge: Identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor. J Immunol 179: 6379–6383PubMedGoogle Scholar
  55. 55.
    Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F (2005) IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 174: 3695–3702PubMedGoogle Scholar
  56. 56.
    Lecart S, Morel F, Noraz N, Pene J, Garcia M, Boniface K, Lecron JC, Yssel H (2002) IL-22, in contrast to IL-10, does not induce Ig production, due to absence of a functional IL-22 receptor on activated human B cells. Int Immunol 14: 1351–1356PubMedCrossRefGoogle Scholar
  57. 57.
    Aggarwal S, Xie MH, Maruoka M, Foster J, Gurney AL (2001) Acinar cells of the pancreas are a target of interleukin-22. J Interferon Cytokine Res 21: 1047–1053PubMedCrossRefGoogle Scholar
  58. 58.
    Parrish-Novak J, Xu W, Brender T, Yao L, Jones C, West J, Brandt C, Jelinek L, Madden K, McKernan PA et al (2002) Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem 277: 47517–47523PubMedCrossRefGoogle Scholar
  59. 59.
    Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC (2002) Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem 277: 33676–33682PubMedCrossRefGoogle Scholar
  60. 60.
    Shalom-Barak T, Quach J, Lotz M (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 273: 27467–27473PubMedCrossRefGoogle Scholar
  61. 61.
    Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J et al (2007) The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol 8: 247–256PubMedCrossRefGoogle Scholar
  62. 62.
    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: 1233–1240PubMedCrossRefGoogle Scholar
  63. 63.
    Huang F, Kao CY, Wachi S, Thai P, Ryu J, Wu R (2007) Requirement for both JAKmediated PI3K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol 179: 6504–6513PubMedGoogle Scholar
  64. 64.
    Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E, Asadullah K, Volk HD, Sterry W, Wolk K (2007) Immunopathogenesis of psoriasis. Exp Dermatol 16: 779–798PubMedCrossRefGoogle Scholar
  65. 65.
    Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S et al (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183: 2593–2603PubMedCrossRefGoogle Scholar
  66. 66.
    Laan M, Cui ZH, Hoshino H, Lotvall J, Sjostrand M, Gruenert DC, Skoogh BE, Linden A (1999) Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J Immunol 162: 2347–2352PubMedGoogle Scholar
  67. 67.
    Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, Fossiez F, Ryffel B, Schnyder B (2006) Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 203: 2715–2725PubMedCrossRefGoogle Scholar
  68. 68.
    Jones CE, Chan K (2002) 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 26: 748–753PubMedGoogle Scholar
  69. 69.
    Kawaguchi M, Kokubu F, Odaka M, Watanabe S, Suzuki S, Ieki K, Matsukura S, Kurokawa M, Adachi M, Huang SK (2004) Induction of granulocyte-macrophage colony-stimulating factor by a new cytokine, ML-1 (IL-17F), via Raf I-MEK-ERK pathway. J Allergy Clin Immunol 114: 444–450PubMedCrossRefGoogle Scholar
  70. 70.
    Schwarzenberger P, La Russa V, Miller A, Ye P, Huang W, Zieske A, Nelson S, Bagby GJ, Stoltz D, Mynatt RL et al (1998) IL-17 stimulates granulopoiesis in mice: Use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines. J Immunol 161: 6383–6389PubMedGoogle Scholar
  71. 71.
    Kao CY, Chen Y, Thai P, Wachi S, Huang F, Kim C, Harper RW, Wu R (2004) IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol 173: 3482–3491PubMedGoogle Scholar
  72. 72.
    Chen Y, Thai P, Zhao YH, Ho YS, DeSouza MM, Wu R (2003) Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop. J Biol Chem 278: 17036–17043PubMedCrossRefGoogle Scholar
  73. 73.
    Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160: 3513–3521PubMedGoogle Scholar
  74. 74.
    Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, Yi J, Guentert T, Tousson A, Stanus AL et al (2008) Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9: 166–175PubMedCrossRefGoogle Scholar
  75. 75.
    Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J et al (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194: 519-527Google Scholar
  76. 76.
    Kelly MN, Kolls JK, Happel K, Schwartzman JD, Schwarzenberger P, Combe C, Moretto M, Khan IA (2005) Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun 73: 617–621PubMedCrossRefGoogle Scholar
  77. 77.
    Huang W, Na L, Fidel PL, Schwarzenberger P (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190: 624–631PubMedCrossRefGoogle Scholar
  78. 78.
    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: 375–387PubMedCrossRefGoogle Scholar
  79. 79.
    Lubberts E, Joosten LA, Oppers B, van den Bersselaar L, Coenen-de Roo CJ, Kolls JK, Schwarzenberger P, van de Loo FA, van denBerg WB (2001) IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 167: 1004–1013PubMedGoogle Scholar
  80. 80.
    Koenders MI, Lubberts E, van de Loo FA, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Kolls JK, Di Padova FE, Joosten LA, van den Berg WB (2006) Interleukin-17 acts independently of TNF-alpha under arthritic conditions. J Immunol 176: 6262–6269PubMedGoogle Scholar
  81. 81.
    Bush KA, Farmer KM, Walker JS, Kirkham BW (2002) Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum 46: 802–805PubMedCrossRefGoogle Scholar
  82. 82.
    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: 566–573PubMedGoogle Scholar
  83. 83.
    Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z et al (2008) Regulation of inflammatory responses by IL-17F. J Exp Med 205: 1063–1075PubMedCrossRefGoogle Scholar
  84. 84.
    Izcue A, Hue S, Buonocore S, Arancibia-Carcamo CV, Ahern PP, Iwakura Y, Maloy KJ, Powrie F (2008) Interleukin-23 restrains regulatory T cell activity to drive T celldependent colitis. Immunity 28: 559–570PubMedCrossRefGoogle Scholar
  85. 85.
    Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls JK (2006) Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis 12: 382–388PubMedCrossRefGoogle Scholar
  86. 86.
    Sonderegger I, Rohn TA, Kurrer MO, Iezzi G, Zou Y, Kastelein RA, Bachmann MF, Kopf M (2006) Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 36: 2849–2856PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Robert Sabat
    • 1
  • Katrin Witte
    • 1
  • Kerstin Wolk
    • 1
  1. 1.Interdisciplinary group of Molecular Immunopathology, Dermatology/Medical ImmunologyUniversity Hospital CharitéBerlinGermany

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