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.

  • Review Article
  • Published:

Targeting IL-17 and TH17 cells in chronic inflammation

Nature Reviews Drug Discovery volume 11, pages 763–776 (2012)Cite this article

Subjects

Key Points

  • Interleukin-17 (IL-17) is a pro-inflammatory cytokine that contributes to the pathogenesis of several inflammatory diseases.

  • The key IL-17 family members are IL-17A and IL-17F, which share a 50% sequence homology. They bind to an IL-17 receptor (IL-17R) complex that is composed of two chains, known as IL-17RA and IL-17RC. IL-17A and IL-17F interact with inflammatory cytokines such as IL-1 and tumour necrosis factor, often in a synergistic manner.

  • IL-17A and IL-17F are the key cytokines produced by T helper 17 (TH17) cells. These cells are crucial for the control of infections, especially extracellular bacterial and fungal infections. They also contribute to epithelial and mucosal protection.

  • Overexpression of IL-17 and TH17 cells contributes to tissue inflammation that is accompanied by matrix destruction, autoimmunity and vascular activation.

  • Positive results have been obtained in clinical trials with two monoclonal antibodies against IL-17A in psoriasis, rheumatoid arthritis and ankylosing spondylitis. Positive results in a clinical trial in psoriasis have been obtained with a monoclonal antibody targeting IL-17RA.

  • Dual inhibitors of IL-17A and IL-17F, of IL-17A and tumour necrosis factor as well as inhibitors of IL-17R signalling are at the preclinical stage of development.

Abstract

The key role of interleukin-17 (IL-17) and T helper 17 (TH17) cells in tissue inflammation, autoimmunity and host defence led to the experimental targeting of these molecules in mouse models of diseases as well as in clinical settings. Moreover, the demonstration that IL-17 and TH17 cells contribute to local and systemic aspects of disease pathogenesis, as well as the finding that the IL-17–TH17 cell pathway is regulated by IL-23, prompted the identification of inhibitors. These inhibitors include biotechnology products that target IL-23 as well as the leading member of the IL-17 family, IL-17A, and one of its receptors, IL-17 receptor A. Several clinical trials of these inhibitors are underway, and positive results have been obtained in psoriasis, rheumatoid arthritis and ankylosing spondylitis. This Review focuses on the current knowledge of the IL-17–TH17 cell pathway to better understand the positive as well as potential negative consequences of targeting them.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Structure of IL-17 and its interaction with IL-17R.
Figure 2: Key functions of IL-17 and its role in inflammation and matrix destruction.
Figure 3: Key functions of the IL-17–TH17 pathway and its role in host defence.
Figure 4: Tools for targeting the IL-17–TH17 pathway.

Similar content being viewed by others

References

  1. Yao, Z. et al. Human IL-17: a novel cytokine derived from T cells. J. Immunol. 155, 5483–5486 (1995). This is the first paper to describe IL-17.

    CAS  PubMed  Google Scholar 

  2. Fossiez, F. et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med. 183, 2593–2603 (1996). This early study describes the role of IL-17 in inflammation.

    Article  CAS  PubMed  Google Scholar 

  3. Rouvier, E., Luciani, M. F., Mattei, M. G., 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. 150, 5445–5456 (1993).

    CAS  PubMed  Google Scholar 

  4. 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). This is one of the first papers to highlight the T H 17 subset of T cells in mice.

    CAS  Google Scholar 

  5. 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 

  6. Bettelli, E., Korn, T. & Kuchroo, V. K. Th17: the third member of the effector T cell trilogy. Curr. Opin. Immunol. 19, 652–657 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M. & Murphy, K. M. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24, 677–688 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Miossec, P., Korn, T. & Kuchroo, V. K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med. 361, 888–898 (2009). This is a review on the clinical aspects of IL-17 and T H 17 cells.

    Article  CAS  PubMed  Google Scholar 

  9. Chabaud, M. et al. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 42, 963–970 (1999). This is the first paper to describe the production of functional IL-17 in chronic inflammation.

    Article  CAS  PubMed  Google Scholar 

  10. Zrioual, S. et al. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J. Immunol. 182, 3112–3120 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Aggarwal, S. & Gurney, A. L. IL-17: prototype member of an emerging cytokine family. J. Leukoc. Biol. 71, 1–8 (2002).

    CAS  PubMed  Google Scholar 

  12. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wright, J. F. et al. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J. Biol. Chem. 282, 13447–13455 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Yang, X. O. et al. Regulation of inflammatory responses by IL-17F. J. Exp. Med. 205, 1063–1075 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chang, S. H. et al. Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 35, 611–621 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, Y. H. 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. 204, 1837–1847 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Yao, Z. et al. Molecular characterization of the human interleukin (IL)-17 receptor. Cytokine 9, 794–800 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Ely, L. K., Fischer, S. & Garcia, K. C. Structural basis of receptor sharing by interleukin 17 cytokines. Nature Immunol. 10, 1245–1251 (2009).

    Article  CAS  Google Scholar 

  22. Rong, Z. et al. IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling. Cell Res. 19, 208–215 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Song, X. et al. IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nature Immunol. 12, 1151–1158 (2011).

    Article  CAS  Google Scholar 

  24. Ramirez-Carrozzi, V. et al. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nature Immunol. 12, 1159–1166 (2011).

    Article  CAS  Google Scholar 

  25. Chang, S. H., Park, H. & Dong, C. Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J. Biol. Chem. 281, 35603–35607 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Qian, Y. et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nature Immunol. 8, 247–256 (2007).

    Article  CAS  Google Scholar 

  27. Hot, A. & Miossec, P. Effects of interleukin (IL)-17A and IL-17F in human rheumatoid arthritis synoviocytes. Ann. Rheum. Dis. 70, 727–732 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Henness, S. et al. IL-17A augments TNF-α-induced IL-6 expression in airway smooth muscle by enhancing mRNA stability. J. Allergy Clin. Immunol. 114, 958–964 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Hartupee, J., Liu, C., Novotny, M., Li, X. & Hamilton, T. IL-17 enhances chemokine gene expression through mRNA stabilization. J. Immunol. 179, 4135–4141 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Shen, F., Hu, Z., Goswami, J. & Gaffen, S. L. Identification of common transcriptional regulatory elements in interleukin-17 target genes. J. Biol. Chem. 281, 24138–24148 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Shi, P. et al. Persistent stimulation with interleukin-17 desensitizes cells through SCFβ-TrCP-mediated degradation of Act1. Sci. Signal. 4, ra73 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Zhu, S. et al. Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling. J. Exp. Med. 207, 2647–2662 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu, C. et al. A CC′ loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Sci. Signal. 4, ra72 (2011).

    PubMed  PubMed Central  Google Scholar 

  34. Kramer, J. M. et al. Evidence for ligand-independent multimerization of the IL-17 receptor. J. Immunol. 176, 711–715 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. 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).

    Article  CAS  PubMed  Google Scholar 

  36. Aggarwal, S., Ghilardi, N., Xie, M. H., de Sauvage, F. J. & Gurney, A. L. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem. 278, 1910–1914 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Happel, K. I. 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. 170, 4432–4436 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. 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).

    Article  CAS  PubMed  Google Scholar 

  39. Langrish, C. L. et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol. Rev. 202, 96–105 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Bettelli, E. et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235–238 (2006). This study shows the balance between T H 17 cells and regulatory T cells in immunopathology.

    Article  CAS  PubMed  Google Scholar 

  43. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  45. Dong, C. Genetic controls of Th17 cell differentiation and plasticity. Exp. Mol. Med. 43, 1–6 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. Sutton, C. E. et al. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31, 331–341 (2009).

    Article  CAS  PubMed  Google Scholar 

  47. Martin, B., Hirota, K., Cua, D. J., Stockinger, B. & Veldhoen, M. Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity 31, 321–330 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Chung, Y. et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576–587 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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).

    Article  CAS  Google Scholar 

  50. Ghoreschi, K. et al. Generation of pathogenic TH17 cells in the absence of TGF-β signalling. Nature 467, 967–971 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 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).

    Article  CAS  PubMed  Google Scholar 

  52. Shibata, K., Yamada, H., Hara, H., Kishihara, K. & Yoshikai, Y. Resident Vδ1+ γδ T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J. Immunol. 178, 4466–4472 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Michel, M. L. et al. Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia. J. Exp. Med. 204, 995–1001 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pichavant, M. et al. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J. Exp. Med. 205, 385–393 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Milpied, P. et al. IL-17-producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression. Blood 118, 2993–3002 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Cua, D. J. & Tato, C. M. Innate IL-17-producing cells: the sentinels of the immune system. Nature Rev. Immunol. 10, 479–489 (2010).

    Article  CAS  Google Scholar 

  57. Ikeda, K. et al. Mast cells produce interleukin-25 upon FcɛRI-mediated activation. Blood 101, 3594–3596 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Mrabet-Dahbi, S., Metz, M., Dudeck, A., Zuberbier, T. & Maurer, M. Murine mast cells secrete a unique profile of cytokines and prostaglandins in response to distinct TLR2 ligands. Exp. Dermatol. 18, 437–444 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Lin, A. M. et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J. Immunol. 187, 490–500 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Hueber, A. J. et al. Mast cells express IL-17A in rheumatoid arthritis synovium. J. Immunol. 184, 3336–3340 (2010).

    Article  CAS  PubMed  Google Scholar 

  61. Moran, E. M. et al. IL-17A expression is localised to both mononuclear and polymorphonuclear synovial cell infiltrates. PLoS ONE 6, e24048 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Noordenbos, T. et al. Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum. 64, 99–109 (2012).

    Article  CAS  PubMed  Google Scholar 

  63. Fiala, M. et al. IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. J. Neuroinflamm. 7, 76 (2010).

    Article  CAS  Google Scholar 

  64. Ge, D. & You, Z. Expression of interleukin-17RC protein in normal human tissues. Int. Arch. Med. 1, 19 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lubberts, E. et al. Requirement of IL-17 receptor signaling in radiation-resistant cells in the joint for full progression of destructive synovitis. J. Immunol. 175, 3360–3368 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Miossec, P. Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum. 48, 594–601 (2003).

    Article  CAS  PubMed  Google Scholar 

  67. Koenders, M. I. et al. Tumor necrosis factor–interleukin-17 interplay induces S100A8, interleukin-1β, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum. 63, 2329–2339 (2011).

    Article  CAS  PubMed  Google Scholar 

  68. van Hamburg, J. P. et al. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 63, 73–83 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Eljaafari, A. et al. Bone marrow- and synovium-derived mesenchymal cells promote Th-17 cells through caspase-1 activation: contribution to rheumatoid arthritis chronicity. Arthritis Rheum. 64, 2147–2157 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Chabaud, M. & Miossec, P. The combination of tumor necrosis factor α blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum. 44, 1293–1303 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Hsu, H. C. et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nature Immunol. 9, 166–175 (2008).

    Article  CAS  Google Scholar 

  72. Toh, M. L. et al. Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression. PLoS ONE 5, e13416 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chabaud, M., Fossiez, F., Taupin, J. L. & Miossec, P. Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J. Immunol. 161, 409–414 (1998).

    CAS  PubMed  Google Scholar 

  74. Schwarzenberger, P. et al. IL-17 stimulates granulopoiesis in mice: use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines. J. Immunol. 161, 6383–6389 (1998).

    CAS  PubMed  Google Scholar 

  75. Schwarzenberger, P. et al. Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis. J. Immunol. 164, 4783–4789 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. McAleer, J. P. & Kolls, J. K. Mechanisms controlling Th17 cytokine expression and host defense. J. Leukoc. Biol. 90, 263–270 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Forlow, S. B. et al. Increased granulopoiesis through interleukin-17 and granulocyte colony-stimulating factor in leukocyte adhesion molecule-deficient mice. Blood 98, 3309–3314 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  80. Kolls, J. K., McCray, P. B. Jr & Chan, Y. R. Cytokine-mediated regulation of antimicrobial proteins. Nature Rev. Immunol. 8, 829–835 (2008). This is a review on the role of IL-17 in antimicrobial host defence.

    Article  CAS  Google Scholar 

  81. 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).

    Article  CAS  PubMed  Google Scholar 

  82. Conti, H. R. et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206, 299–311 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schwarzenberger, P. & Kolls, J. K. Interleukin 17: an example for gene therapy as a tool to study cytokine mediated regulation of hematopoiesis. J. Cell Biochem. 85 (Suppl. 38), 88–95 (2002).

    Article  CAS  Google Scholar 

  84. Ishigame, H. et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30, 108–119 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Cho, J. S. et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J. Clin. Invest. 120, 1762–1773 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Rudner, X. L., Happel, K. I., Young, E. A. & Shellito, J. E. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun. 75, 3055–3061 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wuthrich, M. et al. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J. Clin. Invest. 121, 554–568 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Puel, A. et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332, 65–68 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zelante, T. et al. Sensing of mammalian IL-17A regulates fungal adaptation and virulence. Nature Commun. 3, 683 (2012).

    Article  CAS  Google Scholar 

  90. Aujla, S. J. et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nature Med. 14, 275–281 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. Cooper, A. M. & Khader, S. A. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol. Rev. 226, 191–204 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lin, Y. et al. Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 31, 799–810 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 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).

    Article  CAS  Google Scholar 

  94. Lubberts, E. et al. Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm. Res. 51, 102–104 (2002).

    Article  CAS  PubMed  Google Scholar 

  95. Lubberts, E. et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 50, 650–659 (2004).

    Article  CAS  PubMed  Google Scholar 

  96. Koenders, M. I. et al. Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis. Arthritis Rheum. 52, 3239–3247 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Koenders, M. I. et al. Interleukin-17 acts independently of TNF-α under arthritic conditions. J. Immunol. 176, 6262–6269 (2006).

    Article  CAS  PubMed  Google Scholar 

  98. Krueger, G. G. et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N. Engl. J. Med. 356, 580–592 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Capon, F. et al. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum. Genet. 122, 201–206 (2007).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  101. Zaba, L. C. et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J. Exp. Med. 204, 3183–3194 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kryczek, I. et al. Induction of IL-17+ T cell trafficking and development by IFN-γ: mechanism and pathological relevance in psoriasis. J. Immunol. 181, 4733–4741 (2008).

    Article  CAS  PubMed  Google Scholar 

  103. Lowes, M. A. et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J. Invest. Dermatol. 128, 1207–1211 (2008).

    Article  CAS  PubMed  Google Scholar 

  104. Pene, J. et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J. Immunol. 180, 7423–7430 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Harper, E. G. et al. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J. Invest. Dermatol. 129, 2175–2183 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Appel, H. et al. Analysis of IL-17+ cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res. Ther. 13, R95 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Fisher, S. A. et al. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nature Genet. 40, 710–712 (2008).

    Article  CAS  PubMed  Google Scholar 

  108. Dubinsky, M. C. et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm. Bowel Dis. 13, 511–515 (2007).

    Article  PubMed  Google Scholar 

  109. Kobayashi, T. et al. IL-23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease. Gut 57, 1682–1689 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Yen, D. et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310–1316 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Elson, C. O. et al. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132, 2359–2370 (2007).

    Article  CAS  PubMed  Google Scholar 

  112. O'Connor, W. Jr et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nature Immunol. 10, 603–609 (2009).

    Article  CAS  Google Scholar 

  113. Marotte, H., Charrin, J. E. & Miossec, P. Infliximab-induced aseptic meningitis. Lancet 358, 1784 (2001).

    Article  CAS  PubMed  Google Scholar 

  114. Fromont, A., De Seze, J., Fleury, M. C., Maillefert, J. F. & Moreau, T. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine 45, 55–57 (2009).

    Article  CAS  PubMed  Google Scholar 

  115. Ifergan, I. et al. The blood–brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain 131, 785–799 (2008).

    Article  PubMed  Google Scholar 

  116. Uyttenhove, C. & Van Snick, J. Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis. Eur. J. Immunol. 36, 2868–2874 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  118. Naranjo, A. et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res. Ther. 10, R30 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Roman, M. J. et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N. Engl. J. Med. 349, 2399–2406 (2003).

    Article  CAS  PubMed  Google Scholar 

  120. Greenberg, J. D. et al. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann. Rheum. Dis. 70, 576–582 (2011).

    Article  PubMed  Google Scholar 

  121. Hot, A., Lenief, V. & Miossec, P. Combination of IL-17 and TNFα induces a pro-inflammatory, pro-coagulant and pro-thrombotic phenotype in human endothelial cells. Ann. Rheum. Dis. 71, 768–776 (2012).

    Article  CAS  PubMed  Google Scholar 

  122. Marder, W. et al. Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis. Ann. Rheum. Dis. 70, 1550–1555 (2011).

    Article  CAS  PubMed  Google Scholar 

  123. Hashmi, S. & Zeng, Q. T. Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. Coron. Artery Dis. 17, 699–706 (2006).

    Article  PubMed  Google Scholar 

  124. Eid, R. E. et al. Interleukin-17 and interferon-γ are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation 119, 1424–1432 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. van Es, T. et al. Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochem. Biophys. Res. Commun. 388, 261–265 (2009).

    Article  CAS  PubMed  Google Scholar 

  126. Smith, E. et al. Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice. Circulation 121, 1746–1755 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Chen, S. et al. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice. J. Immunol. 185, 5619–5627 (2010).

    Article  CAS  PubMed  Google Scholar 

  128. McAllister, F. et al. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol. 175, 404–412 (2005).

    Article  CAS  PubMed  Google Scholar 

  129. Ivanov, S., Palmberg, L., Venge, P., Larsson, K. & Linden, A. Interleukin-17A mRNA and protein expression within cells from the human bronchoalveolar space after exposure to organic dust. Respir. Res. 6, 44 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Bullens, D. M. et al. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir. Res. 7, 135 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. McKinley, L. et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J. Immunol. 181, 4089–4097 (2008).

    Article  CAS  PubMed  Google Scholar 

  132. Lajoie, S. et al. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nature Immunol. 11, 928–935 (2010).

    Article  CAS  Google Scholar 

  133. Al-Ramli, W. et al. TH17-associated cytokines (IL-17A and IL-17F) in severe asthma. J. Allergy Clin. Immunol. 123, 1185–1187 (2009).

    Article  CAS  PubMed  Google Scholar 

  134. Tan, H. L. et al. The Th17 pathway in cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 184, 252–258 (2011).

    Article  CAS  PubMed  Google Scholar 

  135. Chen, K. et al. IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLoS ONE 6, e20333 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Di Stefano, A. et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin. Exp. Immunol. 157, 316–324 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Doe, C. et al. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 138, 1140–1147 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Chang, Y. et al. CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease. Respir. Res. 12, 43 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Chu, S. et al. The expression of Foxp3 and ROR gamma t in lung tissues from normal smokers and chronic obstructive pulmonary disease patients. Int. Immunopharmacol. 11, 1780–1788 (2011).

    Article  CAS  PubMed  Google Scholar 

  140. Shan, M. et al. Cigarette smoke induction of osteopontin (SPP1) mediates TH17 inflammation in human and experimental emphysema. Sci. Transl. Med. 4, 117ra119 (2012).

    Article  CAS  Google Scholar 

  141. Simonian, P. L. et al. Th17-polarized immune response in a murine model of hypersensitivity pneumonitis and lung fibrosis. J. Immunol. 182, 657–665 (2009).

    Article  CAS  PubMed  Google Scholar 

  142. Joshi, A. D. et al. Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis. Am. J. Respir. Crit. Care Med. 179, 705–716 (2009).

    Article  CAS  PubMed  Google Scholar 

  143. Wilson, M. S. et al. Bleomycin and IL-1β-mediated pulmonary fibrosis is IL-17A dependent. J. Exp. Med. 207, 535–552 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Mi, S. et al. Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGF-β1-dependent and -independent mechanisms. J. Immunol. 187, 3003–3014 (2011).

    Article  CAS  PubMed  Google Scholar 

  145. Wong, C. K. et al. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin. Immunol. 127, 385–393 (2008).

    Article  CAS  PubMed  Google Scholar 

  146. Tartour, E. et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res. 59, 3698–3704 (1999).

    CAS  PubMed  Google Scholar 

  147. Chevrel, G. et al. Interleukin-17 increases the effects of IL-1β on muscle cells: arguments for the role of T cells in the pathogenesis of myositis. J. Neuroimmunol. 137, 125–133 (2003).

    Article  CAS  PubMed  Google Scholar 

  148. Abdulahad, W. H., Stegeman, C. A., Limburg, P. C. & Kallenberg, C. G. Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 58, 2196–2205 (2008).

    Article  PubMed  Google Scholar 

  149. Zou, W. & Restifo, N. P. TH17 cells in tumour immunity and immunotherapy. Nature Rev. Immunol. 10, 248–256 (2010).

    Article  CAS  Google Scholar 

  150. Garber, K. Newsmaker: lycera. Nature Biotech. 29, 679 (2011).

    Article  CAS  Google Scholar 

  151. Huh, J. R. et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature 472, 486–490 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Solt, L. A. et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472, 491–494 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Xu, T. et al. Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORγ t protein. J. Biol. Chem. 286, 22707–22710 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Haylock-Jacobs, S. et al. PI3Kδ drives the pathogenesis of experimental autoimmune encephalomyelitis by inhibiting effector T cell apoptosis and promoting Th17 differentiation. J. Autoimmun. 36, 278–287 (2011).

    Article  CAS  PubMed  Google Scholar 

  155. Dhimolea, E. & Reichert, J. M. World Bispecific Antibody Summit, September 27–28, 2011, Boston, MA. MAbs 4, 4–13 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Spriggs, M. K. Interleukin-17 and its receptor. J. Clin. Immunol. 17, 366–369 (1997).

    Article  CAS  PubMed  Google Scholar 

  157. Gaffen, S. L. Structure and signalling in the IL-17 receptor family. Nature Rev. Immunol. 9, 556–567 (2009).

    Article  CAS  Google Scholar 

  158. Zrioual, S. et al. IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood. J. Immunol. 180, 655–663 (2008).

    Article  CAS  PubMed  Google Scholar 

  159. Samson, M. et al. Inhibition of IL-6 function corrects Th17/Treg imbalance in rheumatoid arthritis patients. Arthritis Rheum. 64, 2499–2503 (2012).

    Article  CAS  PubMed  Google Scholar 

  160. Hueber, W. et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci. Transl. Med. 2, 52ra72 (2010). This study describes the clinical effects of an IL-17A-targeted antibody in three inflammatory disorders.

    Article  CAS  PubMed  Google Scholar 

  161. Baeten, D. et al. The anti-IL17A monoclonal antibody secukinumab (AIN457) showed good safety and efficacy in the treatment of active ankylosing spondylitis. Arthritis Rheum. 62, Abstract L3847 (2010).

    Google Scholar 

  162. Genovese, M. C. et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 62, 929–939 (2010). This paper is the first to report on a clinical trial in which IL-17A was targeted.

    Article  CAS  PubMed  Google Scholar 

  163. Papp, K. A. et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N. Engl. J. Med. 366, 1181–1189 (2012). This is the first paper to demonstrate the targeting of IL-17RA.

    Article  CAS  PubMed  Google Scholar 

  164. Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 17 May 2012 (doi:10.1136/gutjnl-2011-301668).

  165. Symons, A., Budelsky, A. L. & Towne, J. E. Are Th17 cells in the gut pathogenic or protective? Mucosal Immunol. 5, 4–6 (2012).

    Article  CAS  PubMed  Google Scholar 

  166. Kolls, J. K., Kanaly, S. T. & Ramsay, A. J. Interleukin-17: an emerging role in lung inflammation. Am. J. Respir. Cell Mol. Biol. 28, 9–11 (2003).

    Article  CAS  PubMed  Google Scholar 

  167. Leonardi, C. et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N. Engl. J. Med. 366, 1190–1199 (2012).

    Article  CAS  PubMed  Google Scholar 

  168. Miossec, P. Interleukin-17 in fashion, at last: ten years after its description, its cellular source has been identified. Arthritis Rheum. 56, 2111–2115 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

P.M.'s work is supported by grants from the Institut Mérieux, the Hospices Civils de Lyon (HCL) and the Institut Universitaire de France (IUF). J.K.K.'s work was supported by the National Heart, Lung, and Blood Institute (NHBLI) grant R37-HL079142.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, University of Lyon 1, Hôpital Edouard Herriot, 5 Place d'Arsonval, Lyon, 69437, France

    Pierre Miossec

  2. Immunogenomics and inflammation research unit EA 4130, University of Lyon 1, Hôpital Edouard Herriot, 5 Place d'Arsonval, Lyon, 69437, France

    Pierre Miossec

  3. Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, Pennsylvania, USA

    Jay K. Kolls

Authors
  1. Pierre Miossec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay K. Kolls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Pierre Miossec or Jay K. Kolls.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Abbott 2011 Annual Report (Financial Review: Part 4)

ClinicalTrials.gov website

Roche Pharmaceuticals Pipeline

Glossary

T helper 17 cells

(TH17 cells). A lineage of CD4+ T cells that are defined by the expression of interleukin-17A (IL-17A) and IL-17F; the development of these cells is controlled by the transcription factors retinoid-related orphan receptor-α (RORA) and RORC.

Cystine knots

Motifs that were first described in nerve growth factor, wherein two disulphide bridges are formed from paired cysteine molecules. This motif conveys protein stability.

CCAAT/enhancer-binding proteins

(C/EBPs). A family of transcription factors that regulate gene expression by interacting with the CCAAT box motif.

CC′ loop region

A region of the cytoplasmic SEFIR domain (named after SEF and a homologous TIR (Toll/IL-1R) domain) of interleukin-17 (IL-17) receptor, defined by the third strand (C) and the third helix (C′).

Memory CD4+ T cells

A putative subpopulation of relatively long-lived CD4+ T cells that have interacted with their cognate antigen.

TH1-associated diseases

Diseases attributed to interferon-γ (IFNγ)-producing CD4+ T cells.

STAT4

Signal transducer and activator of transcription 4; a member of the STAT protein family that is required for the development of T helper 1 (TH1) CD4+ T cells.

STAT6

Signal transducer and activator of transcription 6; a member of the STAT protein family that is required for the development of T helper 2 (TH2) CD4+ T cells.

Naive T cells

T cells that have not interacted with their cognate antigen.

RORC

Retinoid-related orphan receptor-γ. RORC encodes a transcription factor that is expressed in interleukin-17 (IL-17)-producing cells.

γδ T cells

A subset of T cells that express a T cell receptor consisting of a γ- and δ-chain as opposed to an α- and β-chain. These cells are enriched at mucosal surfaces: for example, in the gastrointestinal tract, skin and lung.

Invariant NK cells

(iNK cells). A subset of natural killer (NK) cells that express an invariant T cell receptor.

Fcɛ receptor I

A protein that serves as the high-affinity receptor for immunoglobulin E.

TH2-type responses

Immune responses associated with the T helper 2 (TH2) subset of CD4+ T cells, such as allergy or immune responses to helminth infection.

Acute phase response

An increase in levels of plasma proteins in response to acute inflammation.

Matrix metalloproteinases

A family of zinc-dependent proteases that can degrade extracellular matrix proteins.

Receptor activator of NF-κB ligand

(RANKL). A member of the tumour necrosis factor superfamily expressed on osteoblasts that can activate osteoclasts to mediate bone resorption.

B cells

A subpopulation of lymphocytes that develop in the bone marrow and mediate humoral (that is, antibody-mediated) immunity.

TNF receptor 2

Tumour necrosis factor (TNF) receptor 2 (TNFR2; also known as p75 or TNFRSF1B); a 75 kDa receptor that can bind to TNF and lymphotoxin-α.

Neutrophilia

An increased density of neutrophils in peripheral blood.

Mucosal immunity

Immune responses that occur at mucosal membranes.

Apoe−/− mice

Mice with a homozygous deletion in the apolipoprotein E (Apoe) gene; these mice are a model of hypercholesterolaemia.

ACR20 response rate

The response rate of patients in clinical trials for rheumatoid arthritis who show a 20% decrease in the clinical American College of Rheumatology (ACR) score.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miossec, P., Kolls, J. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11, 763–776 (2012). https://doi.org/10.1038/nrd3794

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd3794

This article is cited by

Search

Advanced 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