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Control of innate immune cells, chronic inflammation and infection by cytokine-producing immune microenvironment

Research Project

Project/Area Number 16H05172
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKyoto University

Principal Investigator

IKUTA Koichi  京都大学, ウイルス・再生医科学研究所, 教授 (90193177)

Co-Investigator(Kenkyū-buntansha) 谷一 靖江  京都大学, 医学研究科, 助教 (50432331)
Research Collaborator CUI Guangwei  
MUKOHIRA Hisa  
Zhu Yuanbo  
OGAWA Makoto  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsリンパ球 / 生体分子 / 発生・分化 / サイトカイン / ストローマ細胞 / NK細胞 / 自然リンパ球 / 免疫学 / 感染症 / リンパ組織 / Tリンパ球 / Bリンパ球 / 骨芽細胞
Outline of Final Research Achievements

Innate immune cells, such as innate lymphoid cells and NK cells, play important roles in allergy and infection. Although the cytokines IL-7 and IL-15 are essential for development and maintenance of innate immune cells, the cells producing these cytokines are not well characterized. By using cell-type specific conditional knockout mice, we revealed the functions of the cytokines produced by each type of stromal cells in bone marrow, thymus, liver and intestines, in development, maintenance and pathogenesis of innate immune cells.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、自然免疫系細胞をサイトカインIL-7とIL-15によって助ける組織内の細胞が同定された。そのため、今後は、アレルギーや自己免疫疾患などの慢性炎症ならびに寄生虫などに対する感染防御などの病態における、自然免疫系細胞の役割の総合的な理解が進むと考えられる。また、将来、IL-7とIL-15を用いて自然免疫系細胞を介して、これらの病態を人為的にコントロールすることにも貢献するであろう。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (33 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 5 results) Remarks (3 results)

  • [Int'l Joint Research] ETH Zurich/Helmholtz Centre for Infection Research(スイス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Parque Tecnologico de Ciencias(スペイン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Kantonsspital St. Gallen/Heinrich Heine University/University of Bern, Bern(スイス、ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Yale University/German Cancer Research Center/University of Leuven(米国、ドイツ、ベルギー)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Notch signaling controls transcription via the recruitment of RUNX1 and MYB to enhancers during T cell development2019

    • Author(s)
      Rodriguez-Caparros, A., Garcia, V., Casal, A, Lopez-Ros, J., Garcia-Mariscal, A., Tani-ichi, S., Ikuta, K., and Hernandez-Munain, C.
    • Journal Title

      J. Immunol.

      Volume: 202 Issue: 8 Pages: 2460-2472

    • DOI

      10.4049/jimmunol.1801650

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tissue maintenance of CMV-specific inflationary memory T cells by IL-152018

    • Author(s)
      Baumann, N., Torti, N., Welten, S. P. M., Barnstorf, I., Borsa, M., Pallmer, K., Oduro, J. D., Cicin-Sain, L., Ikuta, K., Ludewig, B., and Oxenius, A.
    • Journal Title

      PLoS Pathog.

      Volume: 14 Issue: 4 Pages: e1006993-e1006993

    • DOI

      10.1371/journal.ppat.1006993

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR42018

    • 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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells2017

    • Author(s)
      Nakamizo Satoshi、Honda Tetsuya、Adachi Akimasa、Nagatake Takahiro、Kunisawa Jun、Kitoh Akihiko、Otsuka Atsushi、Dainichi Teruki、Nomura Takashi、Ginhoux Florent、Ikuta Koichi、Egawa Gyohei、Kabashima Kenji
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 999-999

    • DOI

      10.1038/s41598-017-14292-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sepsis-induced osteoblast ablation causes immunodeficiency2016

    • Author(s)
      Terashima, A., Okamoto, K., Nakashima, T., Akira, S., Ikuta, K. and Takayanagi, H.
    • Journal Title

      Immunity

      Volume: 44 Issue: 6 Pages: 1434-1443

    • DOI

      10.1016/j.immuni.2016.05.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thy-1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation2016

    • Author(s)
      Shinoda, K., Hirahara, K., Iinuma, T., Ichikawa, T., Suzuki, A. S., Sugaya, K., Tumes, D. J., Yamamoto, H., Hara, T., Tani-ichi, S., Ikuta, K., Okamoto, Y., and Nakayama, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 113 Issue: 20

    • DOI

      10.1073/pnas.1512600113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibroblastic reticular cells regulate intestinal inflammation through IL-15-mediated control of group 1 ILCs2016

    • Author(s)
      Gil-Cruz, C., Perez-Shibayama, C., Onder, L., Chai, Q., Cupovic, J., Cheng, H., Novkovic, M., Lang, P. A., Geuking, M. B., McCoy, K. D., Abe, S., Cui, G., Ikuta, K., Scandella, E., and Ludewig, B.
    • Journal Title

      Nat. Immunol.

      Volume: 17 Issue: 12 Pages: 1388-1396

    • DOI

      10.1038/ni.3566

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation2016

    • 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 Issue: 6 Pages: 1219-1231

    • DOI

      10.1016/j.immuni.2016.11.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Intestinal epithelial cell-derived IL-15 supports the homeostasis of intraepithelial lymphocytes2018

    • Author(s)
      Zhu, Y., Cui, G., and Ikuta, K.
    • Organizer
      The 25th East Asia Joint Symposium on Biomedical Research
    • Related Report
      2018 Annual Research Report
    • 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)
      崔広為、生田宏一
    • Organizer
      Kyoto T Cell Conference 第28回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Local IL-15 dependency of liver-resident ILC12018

    • Author(s)
      Asahi, T., Shimba, A., Cui, G., Abe, S., Zhu, Y., Ejima, A., Takami, D., Tani-ichi, S., Hara, T., and Ikuta, K.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Hematopoietic cell-derived IL-15 supports the development and maintenance of NK, NKT and memory CD8 T cells in bone marrow2018

    • Author(s)
      Abe, S., Hara, T., Cui, G., Asahi, T., and Ikuta, K.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CXCL12-expressing bone marrow stromal cells express adiponectin and are targeted by Adipoq-Cre transgene2018

    • Author(s)
      Mukohira, H., Hara, T., Tani-ichi, S., and Ikuta, K.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Intestinal epithelial cell-derived IL-15 supports the homeostasis of intraepithelial lymphocytes2018

    • Author(s)
      Zhu, Y., Cui, G., Shimba, A., Abe, S., Hara, T., Tani-ichi, S., and Ikuta, K.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of bone marrow IL-7 niche critical for B lymphopoesis2017

    • Author(s)
      原崇裕、生田宏一
    • Organizer
      The 7th International Workshop of Kyoto T Cell Conference
    • Place of Presentation
      芝蘭会館、京都市
    • Year and Date
      2017-03-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glucocorticoids drive circadian changes in T-cell homing and response via IL-7 receptor2017

    • Author(s)
      Shimba, A., and Ikuta, K.
    • Organizer
      Immunology 2017 (AAI)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IL-7Rα signaling upregulates growth hormone signaling-related gene in naive T cells2017

    • Author(s)
      Tani-ichi, S., and Ikuta, K.
    • Organizer
      Keystone Symposium: Integrating Metabolism and Immunity
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Osteoblasts mediate immunosuppression during sepsis by regulating lymphopoiesis2017

    • Author(s)
      Terashima, A., Okamoto, K., Nakashima, T., Ikuta, K., and Takayanagi, H.
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グルココルチコイドはIL-7受容体の発現を介してT細胞の体内分布および活性化の日内変動を制御する2017

    • Author(s)
      岡崎史恵、榛葉旭恒、崔広為、生田宏一
    • Organizer
      ConBio2017(生命科学系学会合同年次大会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Glucocorticoids drive diurnal changes in distribution and response of T cells via IL-7 receptor expression2017

    • Author(s)
      Shimba, A., Cui, G., and Ikuta, K.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Competition between STAT5 and PI3K of the IL-7R modulates T cell and type 2 ILC development in vivo2017

    • Author(s)
      Cui, G., Shimba, A., Zhu, Y., Tani-ichi, S., Hara, T., and Ikuta, K.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Exploring the signals upregulating IL-7Rα expression via NFκB activation in T cells2017

    • Author(s)
      Tani-ichi, S., and Ikuta, K.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [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、大津市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Local function of the IL-15 niche in thymus2016

    • Author(s)
      崔広為、榛葉旭恒、阿部真也、朱媛博、向平妃沙、谷一靖江、原崇裕、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、宜野湾市、沖縄
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of IL-15 niche for NK cells in bone marrow2016

    • 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、宜野湾市、沖縄
    • Related Report
      2016 Annual Research Report
  • [Presentation] Immunodeficiency caused by sepsis-induced osteoblast ablation2016

    • Author(s)
      寺島明日香、岡本一男、審良静男、生田宏一、高柳広
    • 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、宜野湾市、沖縄
    • Related Report
      2016 Annual Research Report
  • [Remarks] ステロイドが免疫力を高める?! -免疫の新たな昼夜サイクルを解明-

    • URL

      http://www.infront.kyoto-u.ac.jp/achievements/post-2986/

    • Related Report
      2017 Annual Research Report
  • [Remarks] ステロイドが免疫力を高める -免疫の新たな昼夜サイクルを解明-

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2017/180124_1.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 多能性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ニッチの同定

    • URL

      http://www.infront.kyoto-u.ac.jp/achievements/post-1160/

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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