Novel regulatory T cells induced and differentiated from CD4 T cells

• Project/Area Number: 17H04040
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Shimizu Akira 京都大学, 医学研究科, 教授 (00162694)
• Co-Investigator(Kenkyū-buntansha): 菅井 学 福井大学, 学術研究院医学系部門, 教授 (90303891)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: CD8T / 免疫寛容 / 慢性炎症 / 免疫反応 / 免疫抑制 / 自己免疫 / T cell / 制御性T細胞 / T細胞

Outline of Final Research Achievements

The acquired immune response is mediated by lymphocytes, which express highly diverse receptors. After lymphocytes specifically recognize the antigen through their specific receptors, immune reactions started. Thus, immune responses of lymphocytes are specific for distinct antigens. This system provides big benefit when invaded by microbes or virus. During the normal course of immune reactions, excessive immune reactions will provide adverse effect. To minimize such kind of adverse effect, existence of antigen-specific immune suppression was proposed, but not clearly demonstrated yet. In this regard, we have found that new CD8T cells derived from CD4 T cells will work as immune regulatory cells at least in some experimental settings. In this project, we intended to develop the monitoring system, which visualize CD4-derived CD8 T cells in vivo, and the depleting method of these cells for evaluating the function of such cells in various immune reactions in vivo.

Academic Significance and Societal Importance of the Research Achievements

免疫反応の正負の制御機構は精力的に解明されてきているが、負の制御機構に関する知見は限られている。最近の知見から特殊なCD8T細胞が抗原特異的免疫抑制反応に関与している事が示唆されているが、そういった機能を持った細胞集団の大部分は未だ同定されていない。本研究では、申請者が見出した新しい制御性T細胞の生体内での機能を明らかにすることを目指しており、この細胞の解析から、免疫反応を制御する新しいメカニズムの発見が期待される。このような研究によってもたらされる免疫抑制機構に関する知見は、様々な過剰な免疫反応によって誘導される自己免疫疾患や過敏症に対する新規治療法の開発にも貢献できると考えられる。

Research Products

• [Journal Article] Induced pluripotent stem cell?based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients (2019)
  • Author(s): Imamura Keiko、Izumi Yuishin、Banno Haruhiko、Uozumi Ryuji、Morita Satoshi、Egawa Naohiro、Ayaki Takashi、、et al.
  • Journal Title: BMJ Open Volume: 9
  • DOI: 10.1136/bmjopen-2019-033131
  • NAID: 120006826750
  • Peer Reviewed / Open Access
• [Journal Article] Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors. (2018)
  • Author(s): Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, Tsukamoto H, Mishima S, Nagata M, Iida M, Tokita Y, Asai M, Shimizu A, Komori T, Harada H, MacDougall M, Sugai M, Bessho K.
  • Journal Title: Sci Rep Volume: 8 Pages: 5169-5169
  • DOI: 10.1038/s41598-018-23515-y
  • NAID: 120006545187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sentinel lymph node biopsy using indocyanine green fluorescence in early-stage breast cancer: a meta-analysis (2017)
  • Author(s): Sugie Tomoharu、Ikeda Takafumi、Kawaguchi Atsushi、Shimizu Akira、Toi Masakazu
  • Journal Title: International Journal of Clinical Oncology Volume: 22 Pages: 11-17
  • DOI: 10.1007/s10147-016-1064-z
  • Peer Reviewed
• [Journal Article] Patterns of clinical practice for sentinel lymph node biopsy in women with node-negative breast cancer: the results of a national survey in Japan (2017)
  • Author(s): Ikeda Takafumi、Sugie Tomoharu、Shimizu Akira、Toi Masakazu
  • Journal Title: Breast Cancer Volume: 24 Pages: 341-344
  • DOI: 10.1007/s12282-016-0720-5
  • Peer Reviewed