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Identification of precursors of innate lymphoid cells

Research Project

Project/Area Number 15K15149
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionHokkaido University (2016-2017)
The University of Tokyo (2015)

Principal Investigator

Sawa Shinichiro  北海道大学, 遺伝子病制御研究所, 准教授 (80611756)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords自然リンパ球 / 分化 / 網羅的遺伝子発現解析 / リンパ節形成 / RANK / RORgt / LTi前駆細胞 / 発生
Outline of Final Research Achievements

Lymphoid Tissue inducer (LTi) cell is a member of group 3 innate lymphoid cell required for lymph node organogenesis. So far, the developmental pathway of LTi cell was not precisely investigated, Additionally, the microenvironment required for the maturation of LTi cell was not identified yet. In this research, using comprehensive transcriptome analysis, I tried to identify factors required for LTi cell maturation in vivo.
In the lymph node anlagen, mesenchymal cells express RANKL and LTi cells express RANK, a receptor for RANKL. In vitro, RANK signal upregulates maturation markers of LTi cells. Moreover, LTi cell specific RANK deficient mice lack all the lymph nodes. From these results, I concluded that RANKL expressed by mesenchymal cells in the lymph node anlagen is the critical factor for the terminal differentiation of LTi cells in vivo.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (35 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (9 results) Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (13 results) (of which Int'l Joint Research: 9 results,  Invited: 4 results) Book (3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] パスツール研究所(フランス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ドイツ癌研究センター(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ベルン大学(スイス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] IMBA(オーストリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Institute Pasteur(フランス)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Deutsches Krebsforschungszentrum(ドイツ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Institute of Molecular Biotechnology(オーストリア)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] ドイツ癌研究センター(ドイツ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] パスツール研究所(フランス)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems2017

    • Author(s)
      Okamoto Kazuo、Nakashima Tomoki、Shinohara Masahiro、Negishi-Koga Takako、Komatsu Noriko、Terashima Asuka、Sawa Shinichiro、Nitta Takeshi、Takayanagi Hiroshi
    • Journal Title

      Physiological Reviews

      Volume: 97 Issue: 4 Pages: 1295-1349

    • DOI

      10.1152/physrev.00036.2016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota.2017

    • Author(s)
      Nagashima K, Sawa S, Nitta T, Tsutsumi M, Okamura T, Penninger JM, Nakashima T, Takayanagi H
    • Journal Title

      Nature Immunology

      Volume: 印刷中 Issue: 6 Pages: 675-682

    • DOI

      10.1038/ni.3732

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.2017

    • Author(s)
      Nagashima K, Sawa S, Nitta T, Prados A, Koliaraki V, Kollias G, Nakashima T, Takayanagi H.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 1 Pages: 437-443

    • DOI

      10.1016/j.bbrc.2017.09.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis.2017

    • Author(s)
      Onder L, Morbe U, Pikor N, Novkovic M, Cheng HW Hehlgans T, Pfeffer K, Becher B, Waisman A, Rulicke T, Gommerman J, Mueller CG, Sawa S. Scandella E, Ludewig B.
    • Journal Title

      Immunity

      Volume: 47(1) Issue: 1 Pages: 80-92

    • DOI

      10.1016/j.immuni.2017.05.008

    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota2017

    • Author(s)
      Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Masanori Tsutsumi, Tadashi Okamura, Josef M. Peninger, Tomoki Nakashima and Hiroshi Takayanagi
    • Journal Title

      Nature Immunology

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteoimmunology: the conceptual framework unifying the immune and skeletal systems2017

    • Author(s)
      Kazuo Okamoto, Tomoki Nakashima, Masahiro Shinohara, Takako Negishi-Koga, Noriko Komatsu, Asuka Terashima, Shinichiro Sawa, Takeshi Nitta, and Hiroshi Takayanagi. Osteoimmunology
    • Journal Title

      Physiological Reviews

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] SLAM-associated protein favors the development of iNKT2 over iNKT17 cells2016

    • Author(s)
      Marie-Laure Michel, Christelle Lenoir, Berangere Massot, Severine Diem, Benoit Pasquier, Shinichiro Sawa, Rachel,Rignault-Bricard, Agnes Lehuen, Gerard Eberl, Andre Veillette, Maria Leite-de-Moraes and Sylvain Latour
    • Journal Title

      European Journal of Immunology

      Volume: 46 Issue: 9 Pages: 2162-74

    • DOI

      10.1002/eji.201646313

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation.2015

    • Author(s)
      Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: - Issue: 6 Pages: 207137-207137

    • DOI

      10.1136/annrheumdis-2014-207137

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] RANKL inhibition prevents autoimmune inflammation in the central nervous system2015

    • Author(s)
      Guerrini M.M, Okamoto K, Komatsu N, Sawa S, Danks L, Penninger J.M, Nakashima T, Takayanagi H.
    • Journal Title

      Immunity

      Volume: 43 Issue: 6 Pages: 1174-1185

    • DOI

      10.1016/j.immuni.2015.10.017

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 免疫組織の構築に必要な間葉系細胞2018

    • Author(s)
      澤 新一郎
    • Organizer
      第2回 Fibrosis
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Mesenchymal organizer cell-derived RANKL induces terminal differentiation of LTi cell2017

    • Author(s)
      Shinichiro Sawa, Eriko Sumiya
    • Organizer
      7th International Workshop of Kyoto T cell Conference
    • Place of Presentation
      芝蘭会館(京都市左京区)
    • Year and Date
      2017-03-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Microenvironment for the lymph node organogenesis2017

    • Author(s)
      Shinichiro Sawa
    • Organizer
      11th International Symposium of The Institute Network “Frontiers in Biomedical Sciences”
    • Place of Presentation
      徳島大学藤井記念ホール(徳島市)
    • Year and Date
      2017-02-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸管3型自然リンパ球の生体内機能解明に向けた新規モデルマウスの開発2017

    • Author(s)
      澤 新一郎
    • Organizer
      第54回生化学会北海道支部会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Mesenchymal organizer cell-derived RANKL induces terminal differentiation of LTi cell in the lymph node anlagen2017

    • Author(s)
      Eriko Sumiya, Sawa Shinichiro
    • Organizer
      4th Lymphoid Tissue Meeting (LT4)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LTi cells integrate mesenchymal cell-derived RANKL essential for lymph node organogenesis.2017

    • Author(s)
      澤 新一郎
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society 2017(ICIS 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A trip to the small world of fetal lymph node2017

    • Author(s)
      澤 新一郎
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal organizer cell-derived RANKL induces terminal differentiation of LTi cell2016

    • Author(s)
      Shinichiro Sawa, Tomoki Nakashima, Hiroshi Takayanagi
    • Organizer
      45th Annual Meeting of Japanese Society for Immunology
    • Place of Presentation
      沖縄コンベンションセンター(宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal organizer cell-derived RANKL induces terminal differentiation of LTi cell2016

    • Author(s)
      Shinichiro Sawa
    • Organizer
      EMBO Conference Innate lymphoid cells-2016
    • Place of Presentation
      Kalkscheune (ドイツ・ベルリン)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規マウスモデルを用いたRORγt陽性リンパ球サブセットの機能評価2016

    • Author(s)
      澤 新一郎
    • Organizer
      第40回日本リンパ学会
    • Place of Presentation
      伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Intestinal homeostasis governed by mesenchymal stroma cells2015

    • Author(s)
      永島一樹、澤新一郎、中島友紀、高柳広
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市白石区)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Revisiting role of LTi cells on lymph node organogenesis2015

    • Author(s)
      澤新一郎、高柳広
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市白石区)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] リンパ節形成におけるRANKL-RANKシグナルの役割2015

    • Author(s)
      澤 新一郎
    • Organizer
      第25回 Kyoto T cell Confeence
    • Place of Presentation
      芝蘭会館(京都市左京区)
    • Year and Date
      2015-05-01
    • Related Report
      2015 Research-status Report
  • [Book] 生体の科学2017

    • Author(s)
      澤 新一郎
    • Total Pages
      5
    • Publisher
      医学書院
    • Related Report
      2017 Annual Research Report
  • [Book] 周産期医学2017

    • Author(s)
      澤 新一郎
    • Total Pages
      6
    • Publisher
      東京医学社
    • Related Report
      2017 Annual Research Report
  • [Book] 炎症と免疫 / RORgt陽性自然リンパ球発生と機能2015

    • Author(s)
      澤 新一郎
    • Total Pages
      6
    • Publisher
      先端医学社
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 標的細胞を欠損した非ヒト動物の作製方法2018

    • Inventor(s)
      澤 新一郎
    • Industrial Property Rights Holder
      澤 新一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-016832
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report
    • Overseas

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Published: 2015-04-16   Modified: 2022-12-28  

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