Regulation of immune microenvironment by IL-15-expressing cells in vivo

• Project/Area Number: 17K15721
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Cui Guangwei 京都大学, ウイルス・再生医科学研究所, 助教 (70791276)
• Research Collaborator: IKUTA Koichi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫微小環境 / サイトカイン / インターロイキン15 / NKT細胞 / ストローマ細胞 / IL-15 / 免疫学 / 免疫分化 / 感染症

Outline of Final Research Achievements

Interleukin-15 (IL-15) is an important cytokine for development and homeostasis of the immune system, and we previously identified a variety of IL-15-expressing cells in vivo. However, the local functions of these IL-15-expressing cells is poorly understood. To address this question, we established eleven types of IL-15 conditional knock out (cKO) mice. This study revealed the local function of IL-15-expressing cells in thymus, bone marrow, lymph node, liver and intestine by using these IL-15 cKO mice. IL-15-expressing cells contribute to the development, maturation, homeostasis and response of immune cells in vivo. Furthermore, IL-15-expressing cells in thymus also contribute to the anti-tumor immunity.

Academic Significance and Societal Importance of the Research Achievements

インターロイキン15（IL-15）は免疫細胞に重要な働きをしている。本研究において、IL-15コンディショナルノックアウトマウスなどを独自に作製した。これらのIL-15関連マウスモデルを用い、生体内の様々な組織におけるIL-15産生性免疫微小環境の局所機能を明らかにした。また、抗がん免疫機能について、胸腺内IL-15産生性免疫微小環境も重要であることを示唆した。
本研究によって、IL-15による免疫細胞の制御機構および生体防御機構に対する新たな知見を得ることができた。がんや慢性炎症、自己免疫疾患などに対するIL-15を標的とする治療薬や治療法の開発に有用であると考えられる。

Research Products

• [Journal Article] Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4 (2018)
  • Author(s): Shimba A, Cui G, Tani-Ichi S, Ogawa M, Abe S, Okazaki F, Kitano S, Miyachi H, Yamada H, Hara T, Yoshikai Y, Nagasawa T, Schütz G, Ikuta K.
  • Journal Title: Immunity Volume: 48 Issue: 2 Pages: 286-298
  • DOI: 10.1016/j.immuni.2018.01.004
  • NAID: 120006401712
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Local IL-15 dependency of liver-resident ILC1 (2018)
  • Author(s): Takuma Asahi
  • Organizer: 第47回日本免疫学会総会・学術会議
• [Presentation] Hematopoietic cell-derived IL-15 supports the development and maintenance of NK, NKT and memory CD8 T cells in bone marrow (2018)
  • Author(s): Shinya Abe
  • Organizer: 第47回日本免疫学会総会・学術会議
• [Presentation] Intestinal epithelial cell-derived IL-15 supports the homeostasis of intraepithelial lymphocytes (2018)
  • Author(s): Yuanbo Zhu
  • Organizer: 第47回日本免疫学会総会・学術会議
• [Presentation] 胸腺内IL-15産生性免疫微小環境の機能解析 (2018)
  • Author(s): 崔 广為
  • Organizer: 第28回Kyoto T Cell Conference
• [Presentation] Competition between STAT5 and PI3K of IL-7R modulates T cell development and homeostasis (2018)
  • Author(s): Guangwei Cui
  • Organizer: 25th East Asia Joint Symposium on Biomedical Research
  • Int'l Joint Research
• [Presentation] 胸腺内IL-15産生性免疫微小環境の機能解析 (2018)
  • Author(s): 崔广為
  • Organizer: 第28回KTCC (Kyoto T Cell Conference)