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, Heung Kyu Lee, Igor Brodsky, Lesley Pasman, Brian Yordy, F. Thomas Wunderlich, Jens C. Brüning, Hongyu Zhao, Ruslan Medzhitov

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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
Issue number1
StatePublished - Jan 16 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


Dive into the research topics of 'Signaling through the adaptor molecule MyD88 in CD4<sup>+</sup> T cells is required to overcome suppression by regulatory T cells'. Together they form a unique fingerprint.

Cite this