Bacteria-Induced Group 2 Innate Lymphoid Cells in the Stomach Provide Immune Protection through Induction of IgA

Immunity. 2020 Apr 14;52(4):635-649.e4. doi: 10.1016/j.immuni.2020.03.002. Epub 2020 Apr 1.


The intestinal microbiota shapes and directs immune development locally and systemically, but little is known about whether commensal microbes in the stomach can impact their immunological microenvironment. Here, we report that group 2 innate lymphoid cells (ILC2s) were the predominant ILC subset in the stomach and show that their homeostasis and effector functions were regulated by local commensal communities. Microbes elicited interleukin-7 (IL-7) and IL-33 production in the stomach, which in turn triggered the propagation and activation of ILC2. Stomach ILC2s were also rapidly induced following infection with Helicobacter pylori. ILC2-derived IL-5 resulted in the production of IgA, which coated stomach bacteria in both specific pathogen-free (SPF) and H. pylori-infected mice. Our study thus identifies ILC2-dependent IgA response that is regulated by the commensal microbiota, which is implicated in stomach protection by eliminating IgA-coated bacteria including pathogenic H. pylori.

Keywords: Helicobacter pylori; ILC2s; IgA; commensal microbiota; stomach immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Female
  • Gastrointestinal Microbiome / immunology*
  • Gene Expression Regulation
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / immunology
  • Helicobacter pylori / pathogenicity*
  • Immunity, Humoral
  • Immunity, Innate
  • Immunoglobulin A / biosynthesis*
  • Interleukin-33 / genetics
  • Interleukin-33 / immunology
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology*
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Primary Cell Culture
  • Signal Transduction
  • Stomach / immunology*
  • Stomach / microbiology
  • Symbiosis / immunology
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*


  • Il33 protein, mouse
  • Immunoglobulin A
  • Interleukin-33
  • Interleukin-5
  • Interleukin-7
  • interleukin-7, mouse