IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens

Nat Immunol. 2011 Oct 12;12(12):1151-8. doi: 10.1038/ni.2155.

Abstract

Interleukin 17 receptor E (IL-17RE) is an orphan receptor of the IL-17 receptor family. Here we show that IL-17RE is a receptor specific to IL-17C and has an essential role in host mucosal defense against infection. IL-17C activated downstream signaling through IL-17RE-IL-17RA complex for the induction of genes encoding antibacterial peptides as well as proinflammatory molecules. IL-17C was upregulated in colon epithelial cells during infection with Citrobacter rodentium and acted in synergy with IL-22 to induce the expression of antibacterial peptides in colon epithelial cells. Loss of IL-17C-mediated signaling in IL-17RE-deficient mice led to lower expression of genes encoding antibacterial molecules, greater bacterial burden and early mortality during infection. Together our data identify IL-17RE as a receptor of IL-17C that regulates early innate immunity to intestinal pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / immunology
  • Cell Line
  • Citrobacter rodentium
  • Colon / immunology
  • Colon / metabolism
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Gene Expression Regulation
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Immunity, Mucosal / genetics
  • Immunity, Mucosal / immunology*
  • Interleukin-17 / metabolism*
  • Interleukin-22
  • Interleukins / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism*
  • Signal Transduction

Substances

  • Antimicrobial Cationic Peptides
  • IL17RA protein, human
  • Interleukin-17
  • Interleukins
  • Receptors, Interleukin-17