Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria

Immunity. 2012 Dec 14;37(6):1061-75. doi: 10.1016/j.immuni.2012.08.024. Epub 2012 Nov 29.

Abstract

Interleukin-22 (IL-22) is central to host protection against bacterial infections at barrier sites. Both innate lymphoid cells (ILCs) and T cells produce IL-22. However, the specific contributions of CD4(+) T cells and their developmental origins are unclear. We found that the enteric pathogen Citrobacter rodentium induced sequential waves of IL-22-producing ILCs and CD4(+) T cells that were each critical to host defense during a primary infection. Whereas IL-22 production by ILCs was strictly IL-23 dependent, development of IL-22-producing CD4(+) T cells occurred via an IL-6-dependent mechanism that was augmented by, but not dependent on, IL-23 and was dependent on both transcription factors T-bet and AhR. Transfer of CD4(+) T cells differentiated with IL-6 in the absence of TGF-β ("Th22" cells) conferred complete protection of infected IL-22-deficient mice whereas transferred Th17 cells did not. These findings establish Th22 cells as an important component of mucosal antimicrobial host defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrobacter rodentium / immunology*
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / mortality
  • Enterobacteriaceae Infections / prevention & control
  • Gene Expression Regulation
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Interleukin-22
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Interleukins / physiology*
  • Mice
  • Mice, Knockout
  • Mucous Membrane / immunology
  • Mucous Membrane / microbiology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-bet Transcription Factor
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Inflammation Mediators
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Aryl Hydrocarbon
  • T-Box Domain Proteins
  • T-bet Transcription Factor