IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung

J Exp Med. 2007 Mar 19;204(3):481-7. doi: 10.1084/jem.20061791. Epub 2007 Mar 12.

Abstract

Interleukin (IL) 31Ralpha (glycoprotein 130-like monocyte receptor and glycoprotein 130-like receptor) heterodimerizes with oncostatin M receptor beta to bind IL-31, a cytokine expressed preferentially by CD4(+) T helper type 2 (Th2) cells. However, the functions of IL-31-IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Ralpha(-/-) mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule alpha(+) cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Ralpha(-/-) mice promoted enhanced ovalbumin-specific CD4(+) T cell proliferation and purified naive CD4(+) T cells from IL-31Ralpha(-/-) mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell- and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4(+) T cell-mediated Th1 responses were normal in IL-31Ralpha(-/-) mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation.

Publication types

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

MeSH terms

  • Acute Disease
  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Inflammation Mediators / metabolism*
  • Inflammation Mediators / physiology
  • Interleukins / metabolism*
  • Lung Diseases, Parasitic / immunology*
  • Lung Diseases, Parasitic / pathology*
  • Lung Diseases, Parasitic / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin / physiology
  • Schistosomiasis mansoni / genetics
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology*

Substances

  • Il31ra protein, mouse
  • Inflammation Mediators
  • Interleukins
  • Receptors, Interleukin
  • interleukin-31, mouse