Analysis of immune microenvironment essential for ILC2 development

• Project/Area Number: 16K08835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Hara Takahiro 京都大学, ウイルス・再生医科学研究所, 助教 (90512301)
• Research Collaborator: Pereira João Pedro ; NAGASAWA Takashi ; SUGIYAMA Tatsuki ; TANI-ICHI Shizue
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 免疫微小環境 / 骨髄微小環境 / 骨髄 / ストローマ細胞 / ILC

Outline of Final Research Achievements

Group 2 innate lymphoid cell (ILC2) play important roles in asthma and parasitic worm infection. ILC2 development heavily depends on IL-7, however, the in vivo source of IL-7 required for ILC2 development is unidentified. In other words, it is unknown where and how ILC2s are generated in vivo.
In this study, we analyzed immune microenvironment essential for ILC2 development. By using IL-7 conditional knockout mice and IL-7 reporter mice, we narrowed down the candidate cells that support ILC2 development.

Academic Significance and Societal Importance of the Research Achievements

本研究は、IL-7遺伝子座に蛍光タンパクGFPをノックインしたマウス及び、ストローマ細胞特異的IL-7遺伝子欠損マウスを用いて、ILC2の分化の場となるIL-7産生性の局所的環境（ニッチ）を明らかにすることを目的とした。本研究成果により、気管支喘息や寄生虫感染症などの疾患に対して、ニッチ細胞特異的にIL-7産生を薬物で調節し、自然リンパ球の発生をコントロールする治療法の開発が可能になると予想される。

Research Products

• [Int'l Joint Research] Yale University School of Medicine(米国)
• [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 Pages: 286-298
  • DOI: 10.1016/j.immuni.2018.01.004
  • NAID: 120006401712
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 多能造血前駆細胞からリンパ球までの分化を方向付ける骨髄IL-7ニッチの同定 (2017)
  • Author(s): 原 崇裕
  • Journal Title: 医学のあゆみ Volume: 261 Pages: 1060-1064
• [Journal Article] Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation (2016)
  • Author(s): Gomes, A. C., Hara, T., Lim, V. Y., Herndler-Brandstetter, D., Nevius, E., Sugiyama, T., Tani-ichi, S., Schlenner, S., Richie, E., Rodewald, H., Flavell, R. A., Nagasawa, T., Ikuta, K., and Pereira, J. P.
  • Journal Title: Immunity Volume: 45 Pages: 1219-1231
  • DOI: 10.1016/j.immuni.2016.11.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Local IL-15 dependency of liver-resident ILC1 (2018)
  • Author(s): Takuma Asahi, Akihiro Shimba, Guangwei Cui, Shinya Abe, Yuanbo Zhu, Aki Ejima, Daichi Takami, Shizue Tani-ichi, Takahiro Hara, Koichi Ikuta
  • Organizer: 日本免疫学会総会・学術集会
• [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, Takahiro Hara, Guangwei Cui, Takuma Asahi, Koichi Ikuta
  • Organizer: 日本免疫学会総会・学術集会
• [Presentation] CXCL12-expressing bone marrow stromal cells express adiponectin and are targeted by Adipoq-Cre transgene (2018)
  • Author(s): Hisa Mukohira, Takahiro Hara, Shizue Tani-ichi, Koichi Ikuta
  • Organizer: 日本免疫学会総会・学術集会
• [Presentation] Intestinal epithelial cell-derived IL-15 supports the homeostasis of intraepithelial lymphocytes (2018)
  • Author(s): Yuanbo Zhu, Guangwei Cui, Akihiro Shimba, Shinya Abe, Takahiro Hara, Shizue Tani-ichi, Koichi Ikuta
  • Organizer: 日本免疫学会総会・学術集会
• [Presentation] Identification of bone marrow IL-7 niche critical for B lymphopoiesis (2017)
  • Author(s): Hara T and Ikuta K
  • Organizer: The 7th International Workshop of Kyoto T Cell Conference
  • Place of Presentation: 京都大学芝蘭会館（京都府・京都市）
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] Identification and characterization of IL-7 niche in vivo (2017)
  • Author(s): Hara T and Ikuta K
  • Organizer: The 11th International Symposium of the Institute Network
  • Place of Presentation: 藤井節郎記念医科学センター（徳島県・徳島市）
  • Year and Date: 2017-01-26
• [Presentation] Identification of IL-15 niche for NK cells in bone marrow (2016)
  • Author(s): 阿部真也、原 崇裕、崔 広為、生田宏一
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-07
• [Presentation] 骨髄におけるリンパ球分化を制御するIL-7産生ストローマ細胞の同定 (2016)
  • Author(s): 原 崇裕、生田宏一
  • Organizer: 第26回Kyoto T Cell Conference
  • Place of Presentation: 延暦寺会館（滋賀県・大津市）
  • Year and Date: 2016-05-20
• [Remarks] 京都大学ウイルス・再生医科学研究所
  • URL: http://www.infront.kyoto-u.ac.jp/
• [Remarks] 京都大学ウイルス・再生医科学研究所 免疫制御分野
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/Ikuta-Lab/index.html