Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation

Cell. 2017 Sep 21;171(1):201-216.e18. doi: 10.1016/j.cell.2017.07.027. Epub 2017 Aug 24.

Abstract

An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). During inflammatory stimulation, ILCregs can be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. Moreover, TGF-β1 is induced by ILCregs during the innate intestinal inflammation, and autocrine TGF-β1 sustains the maintenance and expansion of ILCregs. Therefore, ILCregs play an inhibitory role in the innate immune response, favoring the resolution of intestinal inflammation.

Keywords: IL-10; ILCreg; TGF-β1; intestinal inflammation; regulation.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Colitis / immunology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Humans
  • Immunity, Innate*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Lymphocyte Activation
  • Lymphocytes / cytology*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / cytology*
  • Mucous Membrane / immunology*
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta1 / immunology

Substances

  • Homeodomain Proteins
  • Transforming Growth Factor beta1
  • RAG-1 protein
  • Interleukin-10