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.

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
  • 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
  • interleukin-22