Signaling through the adaptor molecule MyD88 in CD4+ T cells is required to overcome suppression by regulatory T cells

Dominik Schenten, Simone A. Nish, Shuang Yu, Xiting Yan, HeungKyu Lee, Igor Brodsky, Lesley Pasman, Brian Yordy, F. Thomas Wunderlich, Jens C. Brüning, Hongyu Zhao, Ruslan Medzhitov

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Innate immune recognition controls adaptive immune responses through multiple mechanisms. The MyD88 signaling adaptor operates in many cell types downstream of Toll-like receptors (TLRs) and interleukin-1 (IL-1) receptor family members. Cell-type-specific functions of MyD88 signaling remain poorly characterized. Here, we have shown that the Tcell-specific ablation of MyD88 in mice impairs not only T helper 17 (Th17) cell responses, but also Th1 cell responses. MyD88 relayed signals of TLR-induced IL-1, which became dispensable for Th1 cell responses in the absence of T regulatory (Treg) cells. Treg cell-specific ablation of MyD88 had no effect, suggesting that IL-1 acts on naive CD4+ Tcells instead of Treg cells themselves. Together, these findings demonstrate that IL-1 renders naive CD4+ Tcells refractory to Treg cell-mediated suppression in order to allow their differentiation into Th1 cells. In addition, IL-1 was also important for the generation of functional CD4+ memory Tcells.

Original languageEnglish (US)
Pages (from-to)78-90
Number of pages13
JournalImmunity
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 16 2014

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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