Complementarity and redundancy of IL-22-producing innate lymphoid cells

Nat Immunol. 2016 Feb;17(2):179-86. doi: 10.1038/ni.3332. Epub 2015 Nov 30.

Abstract

Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrobacter rodentium / immunology
  • Cluster Analysis
  • Disease Models, Animal
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / metabolism
  • Enterobacteriaceae Infections / mortality
  • Enterobacteriaceae Infections / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Homeostasis
  • Immunity, Innate*
  • Interleukins / biosynthesis*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cell Leukemia Sequence 1 Protein / deficiency
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Signal Transduction
  • T-Box Domain Proteins / deficiency
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcriptome

Substances

  • Interleukins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Natural Cytotoxicity Triggering Receptor 1
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • interleukin-22