Nucleic acid sensing by T cells initiates Th2 cell differentiation

被引：38

作者：

Imanishi, Takayuki ^{[1
]}

Ishihara, Chitose ^{[1
]}

Badr, Mohamed El Sherif Gadelhaq ^{[1
]}

Hashimoto-Tane, Akiko ^{[1
]}

Kimura, Yayoi ^{[2
]}

Kawai, Taro ^{[3
]}

Takeuchi, Osamu ^{[3
]}

Ishii, Ken J. ^{[4
,5
]}

Taniguchi, Shun'ichiro ^{[6
]}

Noda, Tetsuo ^{[7
]}

Hirano, Hisashi ^{[2
]}

Brombacher, Frank ^{[8
]}

Barber, Glen N. ^{[9
,10
]}

Akira, Shizuo ^{[3
]}

Saito, Takashi ^{[1
,11
]}

机构：

[1] RIKEN, Ctr Integrat Med Sci IMS RCAI, Lab Cell Signaling, Yokohama, Kanagawa 2300045, Japan

[2] Yokohama City Univ, Grad Sch Med Life Sci, Yokohama, Kanagawa 2360004, Japan

[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan

[4] Natl Inst Biomed Innovat, Lab Adjuvant Innovat, Ibaraki, Osaka 5670085, Japan

[5] Osaka Univ, WPI Immunol Frontier Res, Labs Vaccine Sci, Suita, Osaka 5650871, Japan

[6] Shinshu Univ, Grad Sch Med, Inst Pathogenesis & Dis Prevent, Dept Mol Oncol, Matsumoto, Nagano 3908621, Japan

[7] Japanese Fdn Canc Res, Canc Res Inst, Dept Cell Biol, Toshima Ku, Tokyo 1708455, Japan

[8] Univ Cape Town, Fac Hlth Sci, Int Ctr Genet Engn & Biotechnol, Cape Town Component & Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa

[9] Univ Miami, Miller Sch Med, Dept Cell Biol, Miami, FL 33136 USA

[10] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[11] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Cell Signaling, Suita, Osaka 5650871, Japan

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

TOLL-LIKE; CUTTING EDGE; DNA SENSOR; INNATE; RESPONSES; IMMUNITY; ADAPTER; IL-4; TLR2; TRANSCRIPTION;

D O I：

10.1038/ncomms4566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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