Cytokine IL-6 is required in Citrobacter rodentium infection-induced intestinal Th17 responses and promotes IL-22 expression in inflammatory bowel disease

Mol Med Rep. 2014 Mar;9(3):831-6. doi: 10.3892/mmr.2014.1898. Epub 2014 Jan 14.

Abstract

Citrobacter rodentium (C. rodentium) infection is a widely used murine model to mimic human enteric bacteria infection and inflammatory bowel disease (IBD). In this model, interleukin (IL)‑17A plays critical roles in increasing chemokine and cytokine production in various tissues to recruit innate cells, including monocytes and neutrophils, to the local site of infection. However, the source of IL‑17A remains unclear, as the majority of cell types produce IL‑17A, including intestinal endothelium cells, innate immune cells and CD4+ T cells in disease development. In the current study, wild‑type B6 mice were treated with C. rodentium and the CD4+ Th17 cell subset was observed as being specifically increased in Peyer's patches (PP), but not in mesenteric draining lymph nodes. Furthermore, the research suggested that the differentiation and activation of Th17 cells in PP were dependent on the inflammatory cytokine IL‑6, as blocking IL‑6 signaling with neutralizing antibodies decreased Th17 cells and resulted in the mice being more susceptible to C. rodentium infection. These results confirmed that the Th17 cell subset was specifically activated in PP and demonstrated that IL‑6 is required in Th17 cell activation, which are important to the clinical treatment of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Cell Differentiation
  • Citrobacter rodentium / physiology
  • Disease Models, Animal
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / mortality
  • Enterobacteriaceae Infections / pathology
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunoglobulin A / metabolism
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-17 / metabolism
  • Interleukin-22
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peyer's Patches / cytology
  • Survival Rate
  • Th17 Cells / cytology
  • Th17 Cells / drug effects
  • Th17 Cells / metabolism*
  • Weight Loss

Substances

  • Antibodies, Neutralizing
  • Immunoglobulin A
  • Interleukin-17
  • Interleukin-6
  • Interleukins