Nucleic acid sensing by T cells initiates Th2 cell differentiation.
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.
Laboratory for Cell Signaling, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
Takayuki
T
Imanishi
Laboratory for Cell Signaling, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
Chitose
C
Ishihara
Laboratory for Cell Signaling, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
Mohamed El Sherif Gadelhaq
Mel S
Badr
Laboratory for Cell Signaling, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
Akiko
A
Hashimoto-Tane
Graduate School of Medical Life Sciences, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
Yayoi
Y
Kimura
1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2].
Taro
T
Kawai
1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2].
Osamu
O
Takeuchi
1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan [2] Laboratories of Vaccine Science, WPI Immunology Frontier Research, Osaka University, Suita, Osaka 565-0871, Japan.
Ken J
KJ
Ishii
Department of Molecular Oncology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
Shun'ichiro
S
Taniguchi
Department of Cell Biology, Cancer Research Institute of the Japanese Foundation of Cancer Research, Toshima-ku, Tokyo 170-8455, Japan.
Tetsuo
T
Noda
Graduate School of Medical Life Sciences, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
Hisashi
H
Hirano
International Center for Genetic Engineering and Biotechnology, Cape Town Component and Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Science, Division of Immunology, University of Cape Town, Cape Town, South Africa.
Frank
F
Brombacher
Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Glen N
GN
Barber
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Shizuo
S
Akira
1] Laboratory for Cell Signaling, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan [2] Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Takashi
T
Saito
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009696:Nucleic Acids / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism*
D009696:Nucleic Acids