RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota

Shinichiro Sawa, Matthias Lochner, Naoko Satoh-Takayama, Sophie Dulauroy, Marion Bérard, Melanie Kleinschek, Daniel Cua, James P. Di Santo, Gérard Eberl

Research output: Contribution to journalArticlepeer-review

386 Citations (Scopus)

Abstract

Lymphoid cells that express the nuclear hormone receptor RORβ 3t 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 (TH 17 cells), as well as innate lymphoid cells (ILCs) such as lymphoid tissueĝ€" inducer (LTi) cells and IL-22-producing NKp46+ cells. Here we show that in contrast to TH 17 cells, both types of RORγ t + 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 RORγ t+ ILCs in intestinal homeostasis. Our data identify a finely tuned equilibrium among intestinal symbionts, adaptive immunity and RORγ t+ ILCs.

Original languageEnglish
Pages (from-to)320-328
Number of pages9
JournalNature Immunology
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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