Regulation of development and function of innate lymphoid cells and intraepithelial lymphocytes

• Project/Area Number: 18K07170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Shinshu University
• Principal Investigator: Taki Shinsuke 信州大学, 学術研究院医学系, 教授 (50262027)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自然リンパ球 / 上皮内リンパ球 / 転写因子 / 粘膜免疫 / ホメオスタシス / 腸管免疫系 / T細胞 / 胸腺 / Tリンパ球

Outline of Final Research Achievements

Studies were carried out on the development, homeostasis and function of intraepithelial lymphocytes (IELs) and innate lymphoid cells (ILCs) distributing mainly in mucosal tissues. As to IELs, by pursuing why mice deficient for the transcription factor IRF-2 had only reduced numbers of intestinal IELs, IRF-2 was suggested to work in the IEL precursor cells particularly during the 'agonist selection' process. Also found was the role for T and B cells in the homeostasis of ILCs in the intestinal lamina propria, possibly competing the niche.

Academic Significance and Societal Importance of the Research Achievements

消化管には、他のリンパ組織とは異なる特殊化したリンパ球が存在し、常在細菌などに対する免疫応答を調節するなどして消化管における恒常性の維持に関わっている。そのような特殊化したリンパ球の仲間である上皮内リンパ球がどのようにして生成されるか、また自然リンパ球と呼ばれる細胞の数がどうやって一定に保たれているかの一端を明らかにした本研究は、消化管の健康に関わる重要なメカニズムである粘膜における自然免疫の制御の理解に貢献するものである。

Research Products

• [Journal Article] Cutting Edge: TAK1 Safeguards Macrophages against Proinflammatory Cell Death (2019)
  • Author(s): Sanjo Hideki、Nakayama Jun、Yoshizawa Takahiro、Fehling Hans Joerg、Akira Shizuo、Taki Shinsuke
  • Journal Title: The Journal of Immunology Volume: 203 Issue: 4 Pages: 783-788
  • DOI: 10.4049/jimmunol.1900202
  • Peer Reviewed
• [Journal Article] Staphylococcal superantigen-like 12 activates murine bone marrow derived mast cells (2019)
  • Author(s): Kobayashi Masato、Kitano Takuma、Nishiyama Saishi、Sanjo Hideki、Onozaki Kikuo、Taki Shinsuke、Itoh Saotomo、Hida Shigeaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 511 Issue: 2 Pages: 350-355
  • DOI: 10.1016/j.bbrc.2019.02.052
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Generation of a common innate lymphoid cell progenitor requires interferon regulatory factor 2 (2019)
  • Author(s): Okubo Yohei、Tokumaru Shigeo、Yamamoto Yuta、Miyagawa Shin-ichi、Sanjo Hideki、Taki Shinsuke
  • Journal Title: International Immunology Volume: - Issue: 8 Pages: 489-498
  • DOI: 10.1093/intimm/dxz019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Staphylococcal α-hemolysin does not induce cell damage in murine mast cells but it augments the degranulation induced by FcεRI cross-linking and ionomycin (2019)
  • Author(s): Hayashi Kazuhito、Itoh Saotomo、Morikawa Arisa、Onozaki Kikuo、Taki Shinsuke、Tsuji Tsutomu、Hida Shigeaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 508 Issue: 1 Pages: 263-269
  • DOI: 10.1016/j.bbrc.2018.11.113
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Water intake increases mesenteric lymph flow and the total flux of albumin, long-chain fatty acids, and IL-22 in rats: new concept of absorption in jejunum (2019)
  • Author(s): Nagashio Sachiho、Ajima Kumiko、Maejima Daisuke、Sanjo Hideki、Kajihara Ryo、Hayashi Moyuru、Watanabe-Asaka Tomomi、Kaidoh Maki、Yokoyama Yumiko、Taki Shinshuke、Kawai Yoshiko、Ohhashi Toshio
  • Journal Title: American Journal of Physiology-Gastrointestinal and Liver Physiology Volume: 316 Issue: 1 Pages: G155-G165
  • DOI: 10.1152/ajpgi.00325.2018
  • Peer Reviewed / Open Access / Int'l Joint Research