Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Induction and effector functions of TH17 cells

Abstract

T helper (TH) cells constitute an important arm of the adaptive immune system because they coordinate defence against specific pathogens, and their unique cytokines and effector functions mediate different types of tissue inflammation. The recently discovered TH17 cells, the third subset of effector T helper cells, have been the subject of intense research aimed at understanding their role in immunity and disease. Here we review emerging data suggesting that TH17 cells have an important role in host defence against specific pathogens and are potent inducers of autoimmunity and tissue inflammation. In addition, the differentiation factors responsible for their generation have revealed an interesting reciprocal relationship with regulatory T (Treg) cells, which prevent tissue inflammation and mediate self-tolerance.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Subsets of T helper cells.
Figure 2: Steps in the differentiation of T H 17 cells.
Figure 3: The developmental pathways of T H 17 cells and FOXP3 + T reg cells require TGF-β signalling and are reciprocally regulated.
Figure 4: Effects of TGF-β in shaping the transcriptional programme of developing T helper cell subsets.

References

  1. Mosmann, T. R. & Coffman, R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145–173 (1989)

    CAS  PubMed  Google Scholar 

  2. Fort, M. M. et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15, 985–995 (2001)

    CAS  PubMed  Google Scholar 

  3. Langrish, C. L. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–240 (2005)

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kolls, J. K. & Linden, A. Interleukin-17 family members and inflammation. Immunity 21, 467–476 (2004)

    CAS  PubMed  Google Scholar 

  5. Gunimaladevi, I., Savan, R. & Sakai, M. Identification, cloning and characterization of interleukin-17 and its family from zebrafish. Fish Shellfish Immunol. 21, 393–403 (2006)

    CAS  PubMed  Google Scholar 

  6. Liang, S. C. et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203, 2271–2279 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Chang, S. H. & Dong, C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res. 17, 435–440 (2007)

    PubMed  Google Scholar 

  8. Liang, S. C. et al. An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J. Immunol. 179, 7791–7799 (2007)

    CAS  PubMed  Google Scholar 

  9. Zheng, Y. et al. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445, 648–651 (2007)

    CAS  PubMed  Google Scholar 

  10. Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448, 484–487 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nurieva, R. et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480–483 (2007)

    ADS  CAS  PubMed  Google Scholar 

  12. Zhou, L. et al. IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunol. 8, 967–974 (2007)

    CAS  Google Scholar 

  13. Chtanova, T. et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J. Immunol. 173, 68–78 (2004)

    CAS  PubMed  Google Scholar 

  14. Ye, P. 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. 194, 519–527 (2001)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Mangan, P. R. et al. Transforming growth factor-β induces development of the TH17 lineage. Nature 441, 231–234 (2006)

    ADS  CAS  PubMed  Google Scholar 

  16. Chung, D. R. et al. CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J. Immunol. 170, 1958–1963 (2003)

    CAS  PubMed  Google Scholar 

  17. Infante-Duarte, C., Horton, H. F., Byrne, M. C. & Kamradt, T. Microbial lipopeptides induce the production of IL-17 in Th cells. J. Immunol. 165, 6107–6115 (2000)

    CAS  PubMed  Google Scholar 

  18. Khader, S. A. et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nature Immunol. 8, 369–377 (2007)

    CAS  Google Scholar 

  19. Huang, W., Na, L., Fidel, P. L. & Schwarzenberger, P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J. Infect. Dis. 190, 624–631 (2004)

    CAS  PubMed  Google Scholar 

  20. van Beelen, A. J. et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27, 660–669 (2007)

    CAS  PubMed  Google Scholar 

  21. Charlton, B. & Lafferty, K. J. The Th1/Th2 balance in autoimmunity. Curr. Opin. Immunol. 7, 793–798 (1995)

    CAS  PubMed  Google Scholar 

  22. Ferber, I. A. et al. Mice with a disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 156, 5–7 (1996)

    CAS  PubMed  Google Scholar 

  23. Becher, B., Durell, B. G. & Noelle, R. J. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 110, 493–497 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Cua, D. J. et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–748 (2003)

    ADS  CAS  PubMed  Google Scholar 

  25. Sato, K. et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J. Exp. Med. 203, 2673–2682 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Nakae, S., Nambu, A., Sudo, K. & Iwakura, Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol. 171, 6173–6177 (2003)

    CAS  PubMed  Google Scholar 

  27. Komiyama, Y. et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 177, 566–573 (2006)

    CAS  PubMed  Google Scholar 

  28. Chabaud, M. et al. Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 42, 963–970 (1999)

    CAS  PubMed  Google Scholar 

  29. Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Med. 8, 500–508 (2002)

    CAS  PubMed  Google Scholar 

  30. Fujino, S. et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52, 65–70 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wilson, N. J. et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nature Immunol. 8, 950–957 (2007)

    CAS  Google Scholar 

  32. Kebir, H. et al. Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nature Med. 13, 1173–1175 (2007)

    CAS  PubMed  Google Scholar 

  33. Ben-Nun, A., Wekerle, H. & Cohen, I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 11, 195–199 (1981)

    CAS  PubMed  Google Scholar 

  34. Lohr, J., Knoechel, B., Wang, J. J., Villarino, A. V. & Abbas, A. K. Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease. J. Exp. Med. 203, 2785–2791 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Zenewicz, L. A. et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27, 647–659 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M. & Stockinger, B. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179–189 (2006)

    CAS  PubMed  Google Scholar 

  37. Bettelli, E. et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235–238 (2006)

    ADS  CAS  PubMed  Google Scholar 

  38. Kulkarni, A. B. et al. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl Acad. Sci. USA 90, 770–774 (1993)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  39. Veldhoen, M., Hocking, R. J., Flavell, R. A. & Stockinger, B. Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nature Immunol. 7, 1151–1156 (2006)

    CAS  Google Scholar 

  40. Li, M. O., Wan, Y. Y. & Flavell, R. A. T. Cell-produced transforming growth factor-β1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26, 579–591 (2007)

    CAS  PubMed  Google Scholar 

  41. Acosta-Rodriguez, E. V. et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nature Immunol. 8, 639–646 (2007)

    CAS  Google Scholar 

  42. Sato, W., Aranami, T. & Yamamura, T. Cutting edge: human Th17 cells are identified as bearing CCR2+CCR5- phenotype. J. Immunol. 178, 7525–7529 (2007)

    CAS  PubMed  Google Scholar 

  43. Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A. & Sallusto, F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunol. 8, 942–949 (2007)

    CAS  Google Scholar 

  44. Evans, H. G., Suddason, T., Jackson, I., Taams, L. S. & Lord, G. M. Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc. Natl Acad. Sci. USA 104, 17034–17039 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen, Z., Tato, C. M., Muul, L., Laurence, A. & O’Shea, J. J. Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum. 56, 2936–2946 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Murphy, K. M. & Reiner, S. L. The lineage decisions of helper T cells. Nature Rev. Immunol. 2, 933–944 (2002)

    CAS  Google Scholar 

  47. Sutton, C., Brereton, C., Keogh, B., Mills, K. H. & Lavelle, E. C. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203, 1685–1691 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Stumhofer, J. S. et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nature Immunol. 8, 1363–1371 (2007)

    CAS  Google Scholar 

  49. McGeachy, M. J. et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nature Immunol. 8, 1390–1397 (2007)

    CAS  Google Scholar 

  50. Oppmann, B. et al. 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, 715–725 (2000)

    CAS  PubMed  Google Scholar 

  51. Kastelein, R. A., Hunter, C. A. & Cua, D. J. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25, 221–242 (2007)

    CAS  PubMed  Google Scholar 

  52. Parham, C. et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 168, 5699–5708 (2002)

    CAS  PubMed  Google Scholar 

  53. Uhlig, H. H. et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25, 309–318 (2006)

    CAS  PubMed  Google Scholar 

  54. Duerr, R. H. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461–1463 (2006)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Park, H. et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunol. 6, 1133–1141 (2005)

    CAS  Google Scholar 

  56. Harrington, L. E. et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunol. 6, 1123–1132 (2005)

    CAS  Google Scholar 

  57. Chen, Z. et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc. Natl Acad. Sci. USA 103, 8137–8142 (2006)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yang, X. O. et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282, 9358–9363 (2007)

    CAS  PubMed  Google Scholar 

  59. Ivanov, I. I. et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006)

    CAS  PubMed  Google Scholar 

  60. Yang, X. O. et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ. Immunity 28, 29–39 (2008)

    CAS  PubMed  Google Scholar 

  61. Laurence, A. et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26, 371–381 (2007)

    CAS  PubMed  Google Scholar 

  62. Mucida, D. et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256–260 (2007)

    ADS  CAS  PubMed  Google Scholar 

  63. Antov, A., Yang, L., Vig, M., Baltimore, D. & Van Parijs, L. Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance. J. Immunol. 171, 3435–3441 (2003)

    CAS  PubMed  Google Scholar 

  64. Coombes, J. L. et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757–1764 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhou, L. et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453, 236–240 (2008)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  66. Du, J., Huang, C., Zhou, B. & Ziegler, S. F. Isoform-specific inhibition of RORα-mediated transcriptional activation by human FOXP3. J. Immunol. 180, 4785–4792 (2008)

    CAS  PubMed  Google Scholar 

  67. Gavin, M. A. et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771–775 (2007)

    ADS  CAS  PubMed  Google Scholar 

  68. Williams, L. M. & Rudensky, A. Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nature Immunol. 8, 277–284 (2007)

    CAS  Google Scholar 

  69. Kleinschek, M. A. et al. IL-25 regulates Th17 function in autoimmune inflammation. J. Exp. Med. 204, 161–170 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Batten, M. et al. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nature Immunol. 7, 929–936 (2006)

    CAS  Google Scholar 

  71. Stumhofer, J. S. et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nature Immunol. 7, 937–945 (2006)

    CAS  Google Scholar 

  72. Awasthi, A. et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nature Immunol. 8, 1380–1389 (2007)

    CAS  Google Scholar 

  73. Liu, S. J. et al. Induction of a distinct CD8 Tnc17 subset by transforming growth factor-β and interleukin-6. J. Leukoc. Biol. 82, 354–360 (2007)

    CAS  PubMed  Google Scholar 

  74. Lockhart, E., Green, A. M. & Flynn, J. L. IL-17 production is dominated by γδ T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 177, 4662–4669 (2006)

    CAS  PubMed  Google Scholar 

  75. Ferretti, S., Bonneau, O., Dubois, G. R., Jones, C. E. & Trifilieff, A. IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger. J. Immunol. 170, 2106–2112 (2003)

    CAS  PubMed  Google Scholar 

  76. Molet, S. et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J. Allergy Clin. Immunol. 108, 430–438 (2001)

    CAS  PubMed  Google Scholar 

  77. Zhou, Q., Desta, T., Fenton, M., Graves, D. T. & Amar, S. Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein. Infect. Immun. 73, 935–943 (2005)

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Yao, Z. et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3, 811–821 (1995)

    CAS  PubMed  Google Scholar 

  79. Kuestner, R. E. et al. Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J. Immunol. 179, 5462–5473 (2007)

    CAS  PubMed  Google Scholar 

  80. Toy, D. et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J. Immunol. 177, 36–39 (2006)

    CAS  PubMed  Google Scholar 

  81. Fossiez, F. et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med. 183, 2593–2603 (1996)

    CAS  PubMed  Google Scholar 

  82. Martel-Pelletier, J., Mineau, F., Jovanovic, D., Di Battista, J. A. & Pelletier, J. P. Mitogen-activated protein kinase and nuclear factor κB together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated proten kinase (MAPKAPK). Arthritis Rheum. 42, 2399–2409 (1999)

    CAS  PubMed  Google Scholar 

  83. Stark, M. A. et al. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22, 285–294 (2005)

    CAS  PubMed  Google Scholar 

  84. Starnes, T. et al. Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J. Immunol. 167, 4137–4140 (2001)

    CAS  PubMed  Google Scholar 

  85. Hymowitz, S. G. 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. 20, 5332–5341 (2001)

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Hurst, S. D. 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. 169, 443–453 (2002)

    CAS  PubMed  Google Scholar 

  87. Wolk, K. & Sabat, R. Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine Growth Factor Rev. 17, 367–380 (2006)

    CAS  PubMed  Google Scholar 

  88. Kotenko, S. V. et al. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rβ) 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, 2725–2732 (2001)

    CAS  PubMed  Google Scholar 

  89. Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O’Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683–765 (2001)

    CAS  PubMed  Google Scholar 

  90. Wolk, K. et al. IL-22 increases the innate immunity of tissues. Immunity 21, 241–254 (2004)

    CAS  PubMed  Google Scholar 

  91. Dumoutier, L., Van Roost, E., Colau, D. & Renauld, J. C. 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, 10144–10149 (2000)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Parrish-Novak, J. et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408, 57–63 (2000)

    ADS  CAS  PubMed  Google Scholar 

  93. Leonard, W. J. & Spolski, R. Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nature Rev. Immunol. 5, 688–698 (2005)

    CAS  Google Scholar 

  94. Takeshita, T. et al. Cloning of the gamma chain of the human IL-2 receptor. Science 257, 379–382 (1992)

    ADS  CAS  PubMed  Google Scholar 

  95. Zeng, R. et al. Synergy of IL-21 and IL-15 in regulating CD8+T cell expansion and function. J. Exp. Med. 201, 139–148 (2005)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  96. Spolski, R. & Leonard, W. J. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu. Rev. Immunol. 26, 57–79 (2008)

    CAS  PubMed  Google Scholar 

  97. Coquet, J. M. et al. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. J. Immunol. 178, 2827–2834 (2007)

    CAS  PubMed  Google Scholar 

  98. Pelletier, M., Bouchard, A. & Girard, D. In vivo and in vitro roles of IL-21 in inflammation. J. Immunol. 173, 7521–7530 (2004)

    CAS  PubMed  Google Scholar 

  99. Manel, N., Unutmaz, D. & Littman, D. R. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgamma. Nat. Immunol advance online publication 10.1038/ni.1610 (4 May 2008)

  100. Yang, L. et al. IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature advance online publication 10.1038/nature07021 (11 May 2008)

Download references

Acknowledgements

This work was supported by grants from the National Multiple Sclerosis Society, the National Institutes of Health, the Juvenile Diabetes Research Foundation Center for Immunological Tolerance at Harvard, and the Deutsche Forschungsgemeinschaft. V.K.K. is the recipient of the Javits Neuroscience Investigator Award from the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vijay K. Kuchroo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bettelli, E., Korn, T., Oukka, M. et al. Induction and effector functions of TH17 cells. Nature 453, 1051–1057 (2008). https://doi.org/10.1038/nature07036

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature07036

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing