Induction of IL-22-Producing CD4+ T Cells by Segmented Filamentous Bacteria Independent of Classical Th17 Cells

Front Immunol. 2021 Sep 8:12:671331. doi: 10.3389/fimmu.2021.671331. eCollection 2021.

Abstract

The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.

Keywords: IL-22; Salmonella infection; Th22 cells; bystander activation of T cells; cytokine knock-in reporter mice; segmented filamentous bacteria (SFB).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Gastrointestinal Microbiome / immunology*
  • Interleukin-22
  • Interleukins / biosynthesis
  • Interleukins / immunology*
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Salmonella typhi
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Typhoid Fever / immunology
  • Typhoid Fever / microbiology

Substances

  • Interleukins