Nucleic acid sensing by T cells initiates Th2 cell differentiation

Takayuki Imanishi, Chitose Ishihara, Mohamed E.l.Sherif G.adelhaq Badr, Akiko Hashimoto-Tane, Yayoi Kimura, Taro Kawai, Osamu Takeuchi, Ken J. Ishii, Shun'ichiro Taniguchi, Tetsuo Noda, Hisashi Hirano, Frank Brombacher, Glen N. Barber, Shizuo Akira, Takashi Saito

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Article number3566
Pages (from-to)3566
Number of pages1
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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