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

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Sawa, Shinichiro | Lochner, Matthias | Satoh-Takayama, Naoko | Dulauroy, Sophie | Berard, Marion | Kleinschek, Melanie | Cua, Daniel J | Di Santo, James P. | Eberl, Gerard

Edité par CCSD ; Nature Publishing Group -

International audience. RORγt+ lymphoid cells are involved in containment of the large intestinal microbiota and defense against pathogens through the production of IL-17 and IL-22. They include adaptive TH17 cells, as well as innate lymphoid cells (ILCs), such as lymphoid tissue inducer (LTi) cells and IL-22-producing NKp46+ cells. We find that, in contrast to TH17 cells, both types of RORγt+ ILCs constitutively produced most of the intestinal IL-22, and that symbiotic microbiota repressed this function through epithelial expression of IL-25. This function was increased in the absence of adaptive immunity and fully restored and required upon epithelial damage, demonstrating a central role for RORγt+ ILCs in intestinal homeostasis. Our data reveal a finely tuned equilibrium between symbionts, adaptive immunity and RORγt+ ILCs.

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