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A protective function for interleukin 17A in T cell–mediated intestinal inflammation

Nature Immunology volume 10, pages 603–609 (2009)Cite this article

Abstract

Interleukin 23 (IL-23) and IL-17 have been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Yet as an important function for IL-23 is emerging, the function of IL-17 in inflammatory bowel disease remains unclear. Here we demonstrate IL-17A-mediated protection in the CD45RBhi transfer model of colitis. An accelerated wasting disease elicited by T cells deficient in IL-17A correlated with higher expression of genes encoding T helper type 1–type cytokines in colon tissue. IL-17A also modulated T helper type 1 polarization in vitro. Furthermore, T cells deficient in the IL-17 receptor elicited an accelerated, aggressive wasting disease relative to that elicited by wild-type T cells in recipient mice. Our data demonstrate a protective function for IL-17 and identify T cells as not only the source but also a target of IL-17 in vivo.

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Figure 1: IL-17A-deficient CD45RBhi T cells induce an aggressive wasting disease in Rag1−/− recipient mice.
Figure 2: IL-17 modulates TH1 differentiation.
Figure 3: IL-17 suppresses the induction of T-bet in maturing TH1 cells.
Figure 4: Il17ra−/− CD45RBhi donor T cells elicit an accelerated wasting disease in Rag1−/− recipients.

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Acknowledgements

We thank G. Tokmoulina for assistance with flow cytometry cell sorting; E. Esplugues for critical reading of the manuscript and comments; A. Lin for assistance with statistical analyses; and F. Manzo for administrative assistance. Supported by the National Multiple Sclerosis Society (W.O.) and the Howard Hughes Medical Institute (R.A.F.).

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Author notes

  1. Terrence Town

    Present address: Present address: Department of Neurosurgery, Biomedical Sciences and Department of Medicine, Maxine Dunitz Neurosurgical Institute Cedars-Sinai Medical Center, Los Angeles, California, USA.,

Authors and Affiliations

  1. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    William O'Connor Jr, Masahito Kamanaka, Terrence Town & Richard A Flavell

  2. Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Carmen J Booth

  3. Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Susumu Nakae & Yoichiro Iwakura

  4. Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jay K Kolls

  5. Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA

    Richard A Flavell

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Contributions

W.O. and R.A.F. designed the study and wrote the manuscript; M.K. provided flow cytometry data, advice and technical guidance; W.O. did all other in vitro and in vivo experimental work; C.J.B. did histopathological scoring analyses; T.T. provided assistance with statistical analyses; Y.I. and S.N. provided Il17a−/− mice; and J.K.K. provided the Il17ra−/− mice.

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Correspondence to Richard A Flavell.

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O'Connor Jr, W., Kamanaka, M., Booth, C. et al. A protective function for interleukin 17A in T cell–mediated intestinal inflammation. Nat Immunol 10, 603–609 (2009). https://doi.org/10.1038/ni.1736

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