Nucleic acid sensing by T cells initiates Th2 cell differentiation

Nat Commun. 2014 Apr 10;5:3566. doi: 10.1038/ncomms4566.

Abstract

While T-cell responses are directly modulated by Toll-like receptor (TLR) ligands, the mechanism and physiological function of nucleic acids (NAs)-mediated T cell costimulation remains unclear. Here we show that unlike in innate cells, T-cell costimulation is induced even by non-CpG DNA and by self-DNA, which is released from dead cells and complexes with antimicrobial peptides or histones. Such NA complexes are internalized by T cells and induce costimulatory responses independently of known NA sensors, including TLRs, RIG-I-like receptors (RLRs), inflammasomes and STING-dependent cytosolic DNA sensors. Such NA-mediated costimulation crucially induces Th2 differentiation by suppressing T-bet expression, followed by the induction of GATA-3 and Th2 cytokines. These findings unveil the function of NA sensing by T cells to trigger and amplify allergic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Chromatin Immunoprecipitation
  • Enzyme-Linked Immunosorbent Assay
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Nucleic Acids / metabolism*
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / metabolism*

Substances

  • Nucleic Acids