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