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The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17–producing effector T helper cells in vivo

Nature Immunology volume 10, pages 314–324 (2009)Cite this article

Abstract

Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17-producing helper T cells (TH-17 cells) and has been linked to many human immune disorders. Here we restricted deficiency in the IL-23 receptor to defined cell populations in vivo to investigate the requirement for IL-23 signaling in the development and function of TH-17 cells in autoimmunity, inflammation and infection. In the absence of IL-23, TH-17 development was stalled at the early activation stage. TH-17 cells failed to downregulate IL-2 and also failed to maintain IL-17 production or upregulate expression of the IL-7 receptor α-chain. These defects were associated with less proliferation; consequently, fewer effector TH-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues.

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Figure 1: Il23ra−/− CD4+ T cells do not accumulate in the inflamed CNS.
Figure 2: Il23ra−/− T cells have lower IL-17 production after T cell priming.
Figure 3: Early activation of TH-17 cells is normal but effector responses are impaired for Il23ra−/− T cells.
Figure 4: Full differentiation of effector TH-17 cells requires IL-23R in vivo.
Figure 5: IL-23 promotes the effector cytokine profile of TH-17.
Figure 6: IL-23R is not required for the development of effector TH1 cells.
Figure 7: Timing of the requirement for IL-23R during TH-17 differentiation.
Figure 8: The proliferation of IL-17+ cells is lower in the absence of IL-23R.

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Acknowledgements

We acknowledge the assistance of B. Desai and S. Jungers with flow cytometry sorting, and C. Diveu and R. Kastelein for discussions.

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Authors and Affiliations

  1. Schering-Plough Biopharma, Palo Alto, 94304, California, USA

    Mandy J McGeachy, Yi Chen, Cristina M Tato, Barbara Joyce-Shaikh, Wendy M Blumenschein, Terrill K McClanahan & Daniel J Cua

  2. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Arian Laurence & John J O'Shea

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  1. Mandy J McGeachy
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Contributions

M.J.M. and D.J.C. designed the experiments and wrote the manuscript; M.J.M. did most of the experiments with assistance from B.J.-S. and Y.C.; C.M.T. did toxoplasma experiments; A.L. and J.J.O. provided Cre-STAT3–knockdown data; and W.M.B. and T.K.M. analyzed gene expression.

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Correspondence to Daniel J Cua.

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Competing interests

M.J.M., Y.C., C.M.T., B.J-S., W.B. T.M. and D.J.C. are employed by Schering-Plough Biopharma.

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McGeachy, M., Chen, Y., Tato, C. et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17–producing effector T helper cells in vivo. Nat Immunol 10, 314–324 (2009). https://doi.org/10.1038/ni.1698

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