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The roles of ILC3 and gammadelta T cells in the development of colitis of the model-mice

Research Project

Project/Area Number 16K19163
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKitasato University

Principal Investigator

ISHIHARA Sayaka  北里大学, 理学部, 助教 (50741865)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸炎 / γδT細胞 / ILC3細胞 / ILC3 / Rap1 / 免疫動態 / 接着カスケード / 免疫学
Outline of Final Research Achievements

Mice having CD4+ cell-specific deletion of Rap1 (Rap1KO mice) developed spontaneous colitis. In this study, we investigated the involvement of innate lymphocytes (γδ T cells and ILC3) in the development of colitis. To examine the roles of γδ T cells for colitis, we crossed Rap1KO mice with TCRδ-/- mice (DKO mice). The reduction in weight and histological scores of colitis were suppressed in DKO mice until 12 weeks of age. These data suggest that γδ T cells play critical role in the promotion of colitis at early phase of onset. Since previous study suggests that ILC3 cells have an important role of intestinal immunity, we examined the cell number and function of ILC3 cells. There was no difference in the cell number and IL-22 production of CD4+ILC3 cells derived from LI-LP and mLN between control and Rap1KO mice before the onset of colitis. These data indicate that ILC3 cells are not involved in the development of colitis.

Academic Significance and Societal Importance of the Research Achievements

大腸炎モデルマウスとして使用されているDSS投与マウスは、大腸粘膜のバリア機能を直接障害することで炎症反応を惹起するため、大腸炎の初期の病態形成に関わる免疫細胞の役割についてはわかっていなかった。今回、我々が独自に開発した大腸炎自然発症モデルマウスを用いた研究で、γδ T細胞が大腸炎初期の病態悪化に関与していることが明らかとなった。今後もこのモデルマウスの解析を進めることで、大腸炎発症機構の一端を明らかにすることが期待できる。

Report

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

    (9 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A new approach for analyzing an adhesive bacterial protein in the mouse gastrointestinal tract using optical tissue clearing2019

    • Author(s)
      Nishiyama K, Sugiyama M, Yamada H, Makino K, Ishihara S, Takaki T, Mukai T, Okada N
    • Journal Title

      Scientific reports

      Volume: 9 Issue: 1 Pages: 4731-4731

    • DOI

      10.1038/s41598-019-41151-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice.2018

    • Author(s)
      Nishikimi A, Koyama YI, Ishihara S, Kobayashi S, Tometsuka C, Kusubata M, Kuwaba K, Hayashida O, Hattori S, Katagiri K
    • Journal Title

      Immunity, inflammation and disease

      Volume: - Issue: 2 Pages: 245-255

    • DOI

      10.1002/iid3.213

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Rap1 regulates active conformation of α4β7 and affinity for MadCAM-12018

    • Author(s)
      Sato T, Ishihara S, Marui R, Nishikimi A, Takagi J, Katagiri K
    • Organizer
      日本免疫学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis.2017

    • Author(s)
      Ishihara S, Mamiyoda M, Sato T, Nishikimi A, Saegusa M, Katagiri K.
    • Organizer
      5th Annual Meeting of the International Cytokine & Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] T cell specific Rap1-deficient mice develop spontaneous colitis.2017

    • Author(s)
      Sato T, Ishihara S, Takagi J, Katagiri K.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] The roles of ILC3 and γδ T cells in the development of colitis of the model-mice.2017

    • Author(s)
      Kikuchi N, Ishihara S, Sato T, Sawa S, Shibata K, Yoshikai Y and Katagiri K.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Regulation of adhesion cascade of naive and effector T cells by Rap1 is critical for mucosal homeostasis2016

    • Author(s)
      1.Ishihara S, Nishikimi A, Umemoto E, Miyasaka M, Saegusa M, Katagiri K
    • 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
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Clathrin-dependent internalization of LFA-1 plays an important role in rear detachment of migrating lymphocytes.2016

    • Author(s)
      Nishikimi A, Ishihara S, Katagiri K.
    • 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
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of guanine nucleotide exchange factor (GEF) for Rap1 crucial for lymphocyte trafficking.2016

    • Author(s)
      Momoi Y, Ishihara S, Nishikimi A, Katagiri K.
    • 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
      2016-12-05
    • Related Report
      2016 Research-status Report

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

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