Understanding of the molecular mechanism for nucleic acid sensing by T cells

• Project/Area Number: 24790489
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: IMANISHI Takayuki 独立行政法人理化学研究所, 統合生命医科学研究センター, 研究員 (10513442)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Th2 / TLR / Th1 / 共刺激 / サイトカイン

Research Abstract

Nucleic acids (NAs) are recognized by Toll-like receptors, RIG-I-like receptors, and inflammasomes and then activate innate immune responses. NAs also induce T cell costimulation upon T cell receptor stimulation, but the mechanism and physiological function of this response remains unclear. Unlike in innate cells, T cell costimulation is induced even 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 induced costimulatory responses. The recognition of NAs and subsequent activation of T cells are independent of all known NA sensors in innate system. We found, crucially, that such NA-mediated costimulation induces Th2 differentiation from naive T cells by suppressing T-bet expression, followed by the induction of GATA-3 and Th2 cytokines. These findings provide unveiled function of NA sensing by T cells to trigger and amplify allergic inflammation.

Research Products

• [Journal Article] Nucleic acid sensing by T cells initiates Th2 cell differentiation (2014)
  • Author(s): Takayuki Imanishi, Chitose Ishihara, Mohamed El Sherif Gadelhaq 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
  • Journal Title: NATURE COMMUNICATIONS Volume: 10 Pages: 1038-1038
  • Peer Reviewed
• [Journal Article] Nucleic acids sensing by T cells initiates Th2 cell differentiation (2014)
  • Author(s): Imanishi T, Ishihara C, Badr Mel S, Hashimoto-Tane A, Kimura Y, Kawai T, Takeuchi O, Ishii KJ, Taniguchi S, Noda T, Hirano H, Brombacher F, Barber GN, Akira S, Saito T
  • Journal Title: Nat Commun. Volume: 10 Pages: 3566-3566
  • DOI: 10.1038/ncomms4566
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Direct recognition of nucleic acids by T cells initiates Th2 cell differentiation (2013)
  • Author(s): 2.今西貴之審良静男斉藤隆
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉市幕張メッセ
  • Year and Date: 2013-12-11
• [Presentation] Nucleic acid - mediated T cell activation through a novel sensing mechanism induces Th2 responses (2013)
  • Author(s): 1.今西貴之審良静男斉藤隆
  • Organizer: 第15回国際免疫学会議
  • Place of Presentation: イタリア・ミラノ
  • Year and Date: 2013-08-26
• [Presentation] Nucleic acid-mediated T cell activation through a novel sensing mechanism induces Th2 responses (2013)
  • Author(s): 今西貴之 審良静男 斉藤隆 他
  • Organizer: 第15回国際免疫学会議
  • Place of Presentation: イタリア・ミラノ
• [Remarks] 研究成果に関するwebページ
  • URL: http://www.riken.jp/pr/press/2014/20140410_1/
• [Remarks] 研究成果に関するwebページ
  • URL: http://www.ifrec.osaka-u.ac.jp/jpn/research/2014/04/20140410-natcommun-saito.php
• [Remarks] 理化学研究所ホームページ
  • URL: http://www.riken.jp/pr/press/2014/20140410_1/