A nonredundant role for T cell-derived interleukin 22 in antibacterial defense of colonic crypts

Immunity. 2022 Mar 8;55(3):494-511.e11. doi: 10.1016/j.immuni.2022.02.003.

Abstract

Interleukin (IL)-22 is central to immune defense at barrier sites. We examined the contributions of innate lymphoid cell (ILC) and T cell-derived IL-22 during Citrobacter rodentium (C.r) infection using mice that both report Il22 expression and allow lineage-specific deletion. ILC-derived IL-22 activated STAT3 in C.r-colonized surface intestinal epithelial cells (IECs) but only temporally restrained bacterial growth. T cell-derived IL-22 induced a more robust and extensive activation of STAT3 in IECs, including IECs lining colonic crypts, and T cell-specific deficiency of IL-22 led to pathogen invasion of the crypts and increased mortality. This reflected a requirement for T cell-derived IL-22 for the expression of a host-protective transcriptomic program that included AMPs, neutrophil-recruiting chemokines, and mucin-related molecules, and it restricted IFNγ-induced proinflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispensable role for IL-22-producing T cells in the protection of the intestinal crypts.

Keywords: AMPs; CD4 T cells; Citrobacter rodentium; IFNγ; IL-22; TNF; chemokines; colonic crypt IECs; colonic surface IECs; innate cells; mucins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Citrobacter rodentium*
  • Enterobacteriaceae Infections*
  • Immunity, Innate
  • Interleukin-22
  • Interleukins / metabolism
  • Intestinal Mucosa
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / metabolism

Substances

  • Anti-Bacterial Agents
  • Interleukins