Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation

Immunity. 2015 Apr 21;42(4):692-703. doi: 10.1016/j.immuni.2015.03.008. Epub 2015 Apr 14.

Abstract

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Asthma / chemically induced
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / pathology
  • Cell Line
  • Citrobacter rodentium / immunology
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / pathology
  • Dysbiosis / chemically induced
  • Dysbiosis / genetics
  • Dysbiosis / immunology*
  • Dysbiosis / pathology
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / pathology
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Gene Expression Regulation
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukins / deficiency
  • Interleukins / genetics
  • Interleukins / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin
  • Protein Binding
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / immunology
  • Signal Transduction
  • Sodium Dodecyl Sulfate

Substances

  • Anti-Bacterial Agents
  • Il17b protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Interleukins
  • Mydgf protein, mouse
  • Receptors, Interleukin-17
  • Sodium Dodecyl Sulfate
  • Ovalbumin