T-cell-specific deletion of gp130 renders the highly susceptible IL-10-deficient mouse resistant to intestinal nematode infection

Eur J Immunol. 2009 Aug;39(8):2173-83. doi: 10.1002/eji.200838710.

Abstract

Gp130 is the common receptor of the IL-6 family of cytokines and is involved in many biological processes, including acute phase response, inflammation and immune reactions. To investigate the role of gp130 under inflammatory conditions, T-cell-specific conditional gp130 mice were first bred to the IL-10-deficient background and were then infected with the gastrointestinal nematode Trichuris muris. While IL-10(-/-) mice were highly susceptible to T. muris, developed a mixed Th1/Th17 response and displayed severe inflammation of the caecum, infection of mice with an additional T-cell-specific deletion of gp130 signalling completely reversed the phenotype. These mice showed an accelerated worm expulsion that was associated with the rapid generation of a strong Th2 immune response and a significant increase in Foxp3-expressing Treg. Therefore, gp130 signalling in T cells regulates a switch between proinflammatory and pathogenic Th1/Th17 cells and regulatory Th2/Treg in vivo. Taken together, the data demonstrate that gp130 signalling in T cells is a positive regulator of inflammatory processes, favouring the Th1/Th17 axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / metabolism*
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Host-Parasite Interactions
  • Immunity, Innate / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Interleukin-17 / metabolism
  • Intestinal Diseases, Parasitic / genetics
  • Intestinal Diseases, Parasitic / immunology*
  • Intestinal Diseases, Parasitic / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / parasitology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Trichinellosis / genetics
  • Trichinellosis / immunology*
  • Trichinellosis / parasitology
  • Trichuris / physiology

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Interleukin-10
  • Cytokine Receptor gp130