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Identification of the bone microenvironment that constructs the innate immune system

Research Project

Project/Area Number 19K07604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionKyoto University

Principal Investigator

Hara Takahiro  京都大学, ウイルス・再生医科学研究所, 助教 (90512301)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨髄 / ストローマ細胞 / 微小環境
Outline of Research at the Start

自然免疫を担当する免疫細胞には様々な種類があるが、これらの分化を支持する骨微小環境(ニッチ)の性状は明らかになっていない。
本研究では、自然免疫細胞の分化に必須なニッチ構成ストローマ細胞を同定し、分化を支持するサイトカイン(生理活性タンパク質)、ケモカイン(免疫細胞の遊走活性を制御する因子)を明らかにすることを目的とする。

Outline of Final Research Achievements

There are various types of immune cells responsible for innate immunity, and they play an important role in pathological conditions such as infectious immune response, antitumor immunity, and inflammatory diseases. However, it is not clear whether there is diversity in the bone marrow microenvironment that supports the differentiation, maintenance, and response of various innate immune cells. In this study, we found that multiple innate immune cells form a unique positioning within the bone marrow, and that the bone marrow has a "functionally compartmentalized microenvironment" that supports the innate immune cells.

Academic Significance and Societal Importance of the Research Achievements

定常状態においては、骨髄ストローマ細胞がその種類によって異なる自然免疫細胞を支持していることが示唆された。また、慢性炎症疾患などの病態モデルにおいては、自然免疫細胞の誘引・繋留に関与する分子の機能が阻害され、自然免疫細胞の骨髄内での挙動や末梢への動員に変化が起きた。病態時において、骨髄ストローマ細胞の性質が変容する結果が得られたことから、骨髄ストローマ細胞は慢性炎症疾患の治療標的となり得る。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results) Presentation (6 results) Remarks (6 results)

  • [Journal Article] The roles of IL-7 and IL-15 in niches for lymphocyte progenitors and immune cells in lymphoid organs2021

    • Author(s)
      Ikuta K, Hara T, Abe S, Asahi T, Takami D, Cui G
    • Journal Title

      Curr. Top. Microbiol. Immunol.

      Volume: 434 Pages: 83-101

    • DOI

      10.1007/978-3-030-86016-5_4

    • ISBN
      9783030860158, 9783030860165
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Innate-like CD27+CD45RBhigh γδ T Cells Require TCR Signaling for Homeostasis in Peripheral Lymphoid Organs.2020

    • Author(s)
      Tani-Ichi S, Wagatsuma K, Hara T, Cui G, Abe S, Miyachi H, Kitano S, Ikuta K.
    • Journal Title

      The Journal of Immunology

      Volume: 204(10) Issue: 10 Pages: 2671-2684

    • DOI

      10.4049/jimmunol.1801243

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-7R-Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis.2020

    • Author(s)
      Cui G, Shimba A, Ma G, Takahara K, Tani-Ichi S, Zhu Y, Asahi T, Abe A, Miyachi H, Kitano S, Hara T, Yasunaga JI, Suwanai H, Yamada H, Matsuoka M, Ueki K, Yoshikai Y, Ikuta K.
    • Journal Title

      The Journal of Immunology

      Volume: 204 Issue: 4 Pages: 844-857

    • DOI

      10.4049/jimmunol.1900456

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mesenchymal stromal cells in bone marrow express adiponectin and are efficiently targeted by an adiponectin promoter-driven Cre transgene.2019

    • Author(s)
      Mukohira H, Hara T, Abe S, Tani-Ichi S, Sehara-Fujisawa A, Nagasawa T, Tobe K, Ikuta K.
    • Journal Title

      International Immunology

      Volume: 31 Issue: 11 Pages: 729-742

    • DOI

      10.1093/intimm/dxz042

    • NAID

      120006872738

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intra-epithelial lymphocytes in the intestine2019

    • Author(s)
      Zhu Yuanbo、Cui Guangwei、Miyauchi Eiji、Nakanishi Yuki、Mukohira Hisa、Shimba Akihiro、Abe Shinya、Tani-ichi Shizue、Hara Takahiro、Nakase Hiroshi、Chiba Tsutomu、Sehara-Fujisawa Atsuko、Seno Hiroshi、Ohno Hiroshi、Ikuta Koichi
    • Journal Title

      International Immunology

      Volume: 32 Issue: 5 Pages: 307-319

    • DOI

      10.1093/intimm/dxz082

    • NAID

      120006846480

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Identification of the gut microenvironment by the cytokine reporter mice2021

    • Author(s)
      Hara T
    • Organizer
      第94回 日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The cytokine-producing immune microenvironment for innate lymphocytes2019

    • Author(s)
      Koichi Ikuta, Guangwei Cui, Shinya Abe, Takuma Asahi, Takahiro Hara
    • Organizer
      第48回 日本免疫学会学術集会(アクトシティ浜松)
    • Related Report
      2019 Research-status Report
  • [Presentation] Function of IL-7Rα in regulatory T cells2019

    • Author(s)
      Shizue Tani-ichi, Hisa Mukohira, Takahiro Hara, Koichi Ikuta
    • Organizer
      第48回 日本免疫学会学術集会(アクトシティ浜松)
    • Related Report
      2019 Research-status Report
  • [Presentation] Estrogens suppress T cell production by a TEC-dependent mechanism2019

    • Author(s)
      Shinya Abe, Aki Ejima, Akihiro Shimba, Mizuki Mori, Guangwei Cui, Takuma Asahi, Daichi Takami, Takahiro Hara, Shizue Tani-ichi, Koichi Ikuta
    • Organizer
      第48回 日本免疫学会学術集会(アクトシティ浜松)
    • Related Report
      2019 Research-status Report
  • [Presentation] Role of local IL-7 in maintenance of lung ILC2s2019

    • Author(s)
      Daichi Takami, Shinya Abe, Akihiro Shimba, Takuma Asahi, Yuanbo Zhu, Aki Ejima, Shizue Tani-ichi, Takahiro Hara, Guangwei Cui, Koichi Ikuta
    • Organizer
      第48回 日本免疫学会学術集会(アクトシティ浜松)
    • Related Report
      2019 Research-status Report
  • [Presentation] NK細胞の分化を支持するIL-15産生性骨髄微小環境の解明2019

    • Author(s)
      阿部真也、原崇裕、崔広為、生田宏一
    • Organizer
      第29回 Kyoto T Cell Conference(芝蘭会館)
    • Related Report
      2019 Research-status Report
  • [Remarks] 京都大学 医生物学研究所

    • URL

      https://www.infront.kyoto-u.ac.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] ウイルス感染研究部門 免疫制御分野

    • URL

      https://www.infront.kyoto-u.ac.jp/laboratory/lab07/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 京都大学ウイルス・再生医科学研究所

    • URL

      https://www.infront.kyoto-u.ac.jp/

    • Related Report
      2020 Research-status Report
  • [Remarks] ウイルス感染研究部門免疫制御分野

    • URL

      https://www.infront.kyoto-u.ac.jp/research/lab07/

    • Related Report
      2020 Research-status Report
  • [Remarks] 京都大学 ウイルス・再生医科学研究所

    • URL

      https://www.infront.kyoto-u.ac.jp/

    • Related Report
      2019 Research-status Report
  • [Remarks] ウイルス感染研究部門 免疫制御分野

    • URL

      https://www.infront.kyoto-u.ac.jp/research/lab07/

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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