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

doi:10.1038/ni.2002

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

Nat Immunol. 2011 Apr;12(4):320-6. doi: 10.1038/ni.2002. Epub 2011 Feb 20.

Authors

Shinichiro Sawa¹, Matthias Lochner, Naoko Satoh-Takayama, Sophie Dulauroy, Marion Bérard, Melanie Kleinschek, Daniel Cua, James P Di Santo, Gérard Eberl

Affiliation

¹ Institut Pasteur, Lymphoid Tissue Development Unit, Paris, France.

PMID: 21336274
DOI: 10.1038/ni.2002

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 (T(H)17 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 T(H)17 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity / immunology
Animals
Antigens, Ly / genetics
Antigens, Ly / metabolism
Female
Flow Cytometry
Homeostasis / immunology
Humans
Interleukin-17 / genetics
Interleukin-17 / metabolism
Interleukin-22
Interleukins / genetics
Interleukins / metabolism
Intestinal Mucosa / metabolism
Intestines / immunology*
Intestines / microbiology
Lymphoid Tissue / cytology
Lymphoid Tissue / immunology*
Lymphoid Tissue / metabolism
Male
Mice
Mice, Knockout
Mice, Transgenic
Natural Cytotoxicity Triggering Receptor 1 / genetics
Natural Cytotoxicity Triggering Receptor 1 / metabolism
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / immunology*
Symbiosis / immunology
Time Factors

Substances

Antigens, Ly
Interleukin-17
Interleukins
Mydgf protein, mouse
Natural Cytotoxicity Triggering Receptor 1
Ncr1 protein, mouse
Nuclear Receptor Subfamily 1, Group F, Member 3