The myeloid differentiation factor 88 (MyD88) is required for CD4 + T cell effector function in a murine model of inflammatory bowel disease

Masayuki Fukata, Keith Breglio, Anli Chen, Arunan S. Vamadevan, Tyralee Goo, David Hsu, Daisy Conduah, Ruliang Xu, Maria T. Abreu

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Abnormal T cell responses to commensal bacteria are involved in the pathogenesis of inflammatory bowel disease. MyD88 is an essential signal transducer for TLRs in response to the microflora. We hypothesized that TLR signaling via MyD88 was important for effector T cell responses in the intestine. TLR expression on murine T cells was examined by flow cytometry. CD4+CD45Rbhigh T cells and/or CD4+CD45Rb lowCD25+ regulatory T cells were isolated and adoptively transferred to RAG1-/- mice. Colitis was assessed by changes in body weight and histology score. Cytokine production was assessed by ELISA. In vitro proliferation of T cells was assessed by [3H]thymidine assay. In vivo proliferation of T cells was assessed by BrdU and CFSE labeling. CD4 +CD45Rbhigh T cells expressed TLR2, TLR4, TLR9, and TLR3, and TLR ligands could act as costimulatory molecules. MyD88-/- CD4+ T cells showed decreased proliferation compared with WT CD4 + T cells both in vivo and in vitro. CD4+CD45Rb high T cells from MyD88-/- mice did not induce wasting disease when transferred into RAG1-/- recipients. Lamina propria CD4+ T cell expression of IL-2 and IL-17 and colonic expression of IL-6 and IL-23 were significantly lower in mice receiving MyD88-/- cells than mice receiving WT cells. In vitro, MyD88-/- T cells were blunted in their ability to secrete IL-17 but not IFN-γ. Absence of MyD88 in CD4+CD45Rbhigh cells results in defective T cell function, especially Th17 differentiation. These results suggest a role for TLR signaling by T cells in the development of inflammatory bowel disease.

Original languageEnglish (US)
Pages (from-to)1886-1894
Number of pages9
JournalJournal of Immunology
Volume180
Issue number3
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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