Elucidating the mechanism of autoimmune induction by self-reactive T and regulatory T cells

• Project/Area Number: 26860331
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Tanaka Atsushi 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00724105)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 免疫自己寛容 / 自己免疫疾患 / 制御性T細胞 / 自己免疫 / ZAP-70 / TCRシグナル

Outline of Final Research Achievements

The aim of this research is to elucidate the molecular mechanism of the induction of autoimmunity as a disequilibrium of regulatory T cells and self-reactive T cells. For this aim, we have developed mice with varying structural alterations of ZAP-70 or quantitative changes in ZAP-70 expression levels to control T-cell receptor signaling levels. In these mice, we have analyzed the development of regulatory T cells and self-reactive T cells as well as their changes in TCR repertoires. We have also analyzed cellular functions of respective subsets in the periphery. Our analyses on these mice have suggested that there is a critical range of TCR signaling leading to spontaneous induction of autoimmunity.

Research Products

• [Journal Article] Regulatory T cells in cancer immunotherapy (2017)
  • Author(s): Tanaka, A., and Sakaguchi, S.
  • Journal Title: Cell Research Volume: 27 Issue: 1 Pages: 109-118
  • DOI: 10.1038/cr.2016.151
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tregは本当にがん免疫療法に役立つのか？ (2017)
  • Author(s): 田中淳、坂口志文
  • Journal Title: 腫瘍内科 Volume: １９ Pages: 41-46
• [Journal Article] Identification of novel and noninvasive biomarkers of acute cellular rejection after liver transplantation by protein microarray (2016)
  • Author(s): Okubo, K., Wada, H., Tanaka, A., Eguchi, E., Hamaguchi, M., Tomokuni, A., Tomimaru, Y., Asaoka, T., Hama, N., Kawamoto, K., Kobayashi, S., Marubashi, S., Nagano, H., Sakaguchi, N., Nishikawa, H., Doki, Y., Mori, M., Sakaguchi, S.
  • Journal Title: Transplant Direct Volume: 2 Issue: 12 Pages: e118-e118
  • DOI: 10.1097/txd.0000000000000630
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunology. Early life Aire. (2015)
  • Author(s): Tanaka A, Sakaguchi S.
  • Journal Title: Science Volume: 348(6234) Issue: 6234 Pages: 506-507
  • DOI: 10.1126/science.aab2998
  • Int'l Joint Research
• [Journal Article] 制御性T細胞の同定とその役割 (2015)
  • Author(s): 田中淳、坂口志文
  • Journal Title: がん分子標的治療 Volume: 13(4) Pages: 66-70
• [Journal Article] Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax) (2015)
  • Author(s): Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC, Xue J, Nimmer P, Jin S, Smith M, Xiao Y, Kovar P, Tanaka A et al.
  • Journal Title: Cell Death and Disease Volume: 6 Issue: 1 Pages: e1590-e1590
  • DOI: 10.1038/cddis.2014.561
  • Peer Reviewed
• [Journal Article] Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease. (2014)
  • Author(s): Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali D, Kappler J, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S.
  • Journal Title: Science Volume: 346 Issue: 6207 Pages: 363-8
  • DOI: 10.1126/science.1259077
  • Peer Reviewed
• [Presentation] Selective control of regulatory T cells through TCR signaling molecule (2016)
  • Author(s): Atsushi Tanaka
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Selective control of regulatory T cells through TCR signaling molecule (2016)
  • Author(s): 田中淳
  • Organizer: 第２６回 Kyoto T Cell Conference
  • Place of Presentation: 滋賀県大津市延暦寺会館
  • Year and Date: 2016-05-20
• [Presentation] 制御性T細胞の特異的なTCRシグナル制御とその応用 (2016)
  • Author(s): 田中淳
  • Organizer: 第１６回 LEGEND Seminar 2016
  • Place of Presentation: 沖縄県那覇市ANAクラウンプラザホテル沖縄
  • Invited
• [Presentation] “Autoimmune range of T cell receptor signaling” (2015)
  • Author(s): Atsushi Tanaka, Shinji Maeda, Takashi Nomura, Satoshi Tanaka, Lin Jin, Shuji Akizuki, Rose Zamoyska, Daron M Standley, Noriko Sakaguchi, Shimon Sakaguchi
  • Organizer: Keystone symposia T Cells: Regulation and Effector Function
  • Place of Presentation: 米国ユタ州 Snowbird
  • Year and Date: 2015-04-01
  • Int'l Joint Research
• [Book] Chronic Inflammation: Mechanisms and Regulation (2016)
  • Author(s): Wing, J., Tanaka, A., Sakaguchi, S.
  • Total Pages: 695
  • Publisher: Springer, Japan