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

Gerard Eberl (1) , Shinichiro Sawa (1) , Matthias Lochner (1) , Naoko Satoh-Takayama (1) , Sophie Dulauroy (1) , Marion Berard (1) , Melanie Kleinschek (1) , Daniel J Cua (1) , James P. Di Santo (1)

1 Développement des Tissus Lymphoïdes

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.

Mots clés: Mucosal immunology; Cytokines; Innate immunity; IL-22; Innate Lymphoid Cells

Gerard Eberl, Shinichiro Sawa, Matthias Lochner, Naoko Satoh-Takayama, Sophie Dulauroy, et al.. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nature Immunology, 2011, ⟨10.1038/ni.2002⟩. ⟨hal-00616224⟩