Abstract
Lymphoid cells that express the nuclear hormone receptor RORγt are involved in containment of the large intestinal microbiota and defense against pathogens through the production of interleukin 17 (IL-17) and IL-22. They include adaptive IL-17-producing helper T cells (TH17 cells), as well as innate lymphoid cells (ILCs) such as lymphoid tissue–inducer (LTi) cells and IL-22-producing NKp46+ cells. Here we show that in contrast to TH17 cells, both types of RORγt+ ILCs constitutively produced most of the intestinal IL-22 and that the symbiotic microbiota repressed this function through epithelial expression of IL-25. This function was greater in the absence of adaptive immunity and was fully restored and required after epithelial damage, which demonstrates a central role for RORγt+ ILCs in intestinal homeostasis. Our data identify a finely tuned equilibrium among intestinal symbionts, adaptive immunity and RORγt+ ILCs.
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Change history
27 February 2011
In the version of this article initially published online, the first sentence of the abstract was incorrect. This sentence should begin “Lymphoid cells that express the nuclear hormone receptor RORγt....” The error has been corrected for the print, PDF and HTML versions of this article.
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Acknowledgements
We thank the members of the Lymphoid Tissue Development Unit for discussions and critical reading of the manuscript; L. Polomack for technical assistance; J. Perez and E. Maranghi for work on germ-free mice; and B. Ryffel for p19-deficient mice. Supported by the Institut Pasteur, the Mairie de Paris, the Agence Nationale de la Recherche, the European Commission, Deutsche Forschungsgemeinschaft (M.L.) and the Schlumberger Foundation (M.L.).
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S.S. and G.E. designed the study and wrote the manuscript; S.S. did most of the experimental work; M.L. contributed to the analysis of T cells and DSS-mediated colitis; N.S.-T. contributed to the analysis of NKp46+ ILCs; S.D. did laser-capture microdissection; M.B. generated germ-free mice; M.K. and D.C. generated and provided IL-25-deficient mice; and J.P.D.S. contributed to data analysis and manuscript writing.
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D.C. and M.K. are employees of Merck Research Laboratories, DNAX Discovery Research.
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Sawa, S., Lochner, M., Satoh-Takayama, N. et al. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol 12, 320–326 (2011). https://doi.org/10.1038/ni.2002
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DOI: https://doi.org/10.1038/ni.2002
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