IL-31-IL-31R interactions limit the magnitude of Th2 cytokine-dependent immunity and inflammation following intestinal helminth infection

J Immunol. 2009 May 15;182(10):6088-94. doi: 10.4049/jimmunol.0802459.

Abstract

IL-31 is a recently identified cytokine made predominantly by CD4(+) Th2 cells and its receptor, IL-31R, is expressed by a number of cell types including monocytes, epithelial cells, and T cells. Originally identified as a potential mediator of inflammation in the skin, we recently reported a novel function for endogenous IL-31R interactions in limiting type 2 inflammation in the lung. However, whether IL-31-IL-31R interactions regulate immunity or inflammation at other mucosal sites, such as the gut, is unknown. In this study, we report a regulatory role for IL-31-IL-31R interactions in the intestine following infection with the gastrointestinal helminth Trichuris muris, immunity to which is critically dependent on CD4(+) Th2 cells that produce IL-4 and IL-13. IL-31Ralpha was constitutively expressed in the colon and exposure to Trichuris induced the expression of IL-31 in CD4(+) T cells. In response to Trichuris infection, IL-31Ralpha(-/-) mice exhibited increased Th2 cytokine responses in the mesenteric lymph nodes and elevated serum IgE and IgG1 levels compared with wild type mice. IL-31Ralpha(-/-) mice also displayed enhanced goblet cell hyperplasia and a marked increase in secretion of goblet cell-derived resistin-like molecule beta into the intestinal lumen. Consistent with their exacerbated type 2 inflammatory responses, IL-31Ralpha(-/-) mice exhibited accelerated expulsion of Trichuris with significantly decreased worm burdens compared with their wild type counterparts early following infection. Collectively, these data provide the first evidence of a function for IL-31-IL-31R interactions in limiting the magnitude of type 2 inflammatory responses within the intestine.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Blotting, Western
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Goblet Cells / immunology
  • Goblet Cells / metabolism
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Intestinal Diseases, Parasitic / immunology*
  • Intestinal Diseases, Parasitic / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin / immunology*
  • Receptors, Interleukin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Trichuriasis / immunology*
  • Trichuriasis / metabolism

Substances

  • Cytokines
  • Il31ra protein, mouse
  • Immunoglobulin G
  • Interleukins
  • Receptors, Interleukin
  • interleukin-31, mouse
  • Immunoglobulin E