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Development of targeted therapy against sepsis

Research Project

Project/Area Number 17H04362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

Honda Shin-ichiro  筑波大学, 生存ダイナミクス研究センター, 客員研究員 (60360640)

Co-Investigator(Kenkyū-buntansha) 田原 聡子  筑波大学, 生存ダイナミクス研究センター, 講師 (20360589)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords敗血症 / TLR4 / IL-10 / アラジン-1 / アラジンー1 / TLR / SHP-1 / Toll-like receptor / 感染症 / Allergin-1
Outline of Final Research Achievements

It is important to establish the therapeutic strategy against sepsis by inhibiting hyperactivation of infllammation with controlling infection. An immunoinhibitory receptor, Allergin-1, is expressed on myeloid cells, transmit an inhibitory signal via ITIM sequence in its cytoplasmic region, and function as immune-checkpoint receptor. We found that Allergin-1-deficiency protects the mice from death by cecal ligation puncture (CLP)-induced sepsis. Further analyses demonstrated that Allergin-1-deficiency promotes IL-10 production by peritoneal macrophages via TLR4 signaling. These observations suggest that Allergin-1 may be a therapeutic targeting molecule in sepsis.

Academic Significance and Societal Importance of the Research Achievements

敗血症の治療法は確立しておらず、新たな治療法を開発することが重要である。アラジン-1は免疫応答を制御する免疫チェックポイント分子の1つであるがアラジン-1遺伝子が欠損したマウスでは敗血症誘導後の生存率が亢進することを見出した。アラジン-1は炎症反応を抑制すると仮説を立てたが、予想外に、アラジン-1遺伝子が欠損すると腹腔マクロファージからIL-10産生が亢進し、炎症反応を抑制した。しかし、腹腔内の細菌量には変化がなかった。このことから、アラジン-1を治療標的とすることで、細菌の排除には影響せずに炎症反応だけ抑制できる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017 Other

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Allergin-1 immunoreceptor suppresses house dust mite-induced allergic airway inflammation.2020

    • Author(s)
      Miki H, Tahara-Hanaoka S, Almeida MS, Hitomi K, Shibagaki S, Kanemaru K, Lin YH, Iwata K, Miyake S, Shibayama S, Sumida T, Shibuya K, Shibuya A
    • Journal Title

      Journal of Immunology

      Volume: 204(4) Issue: 4 Pages: 753-762

    • DOI

      10.4049/jimmunol.1900180

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clec10a regulates mite-induced dermatitis2019

    • Author(s)
      Kanemaru K, Noguchi E, Tahara-Hanaoka S, Mizuno S, Tateno H, Denda-Nagai K, Irimura T, Matsuda H, Sugiyama F, Takahashi S, Shibuya K, Shibuya A
    • Journal Title

      Science Immunology,

      Volume: 4(42) Issue: 42 Pages: 6908-6908

    • DOI

      10.1126/sciimmunol.aax6908

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice2019

    • Author(s)
      Lin Yu-Hsien、Tahara-Hanaoka Satoko、Nagai Kei、Yoshikawa Soichiro、Kubo Masato、Shibayama Shiro、Karasuyama Hajime、Shibuya Akira
    • Journal Title

      International Immunology

      Volume: 32 Issue: 3 Pages: 213-219

    • DOI

      10.1093/intimm/dxz075

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression and function of DNAM-1 on human B-lineage cells2019

    • Author(s)
      Nagayama-Hasegawa Y., Honda S, Shibuya A., Shibuya K.
    • Journal Title

      Clinical Cytometry

      Volume: - Issue: 4 Pages: 1-7

    • DOI

      10.1002/cyto.b.21859

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allergy inhibitory receptor‐1 inhibits autoantibody production via upregulation of apoptotic debris clearance by macrophages2018

    • Author(s)
      Iizuka Akira、Segawa Seiji、Kondo Yuya、Kaneko Shunta、Yokosawa Masahiro、Furuyama Kotona、Miki Haruka、Tahara‐Hanaoka Satoko、Shibuya Akira、Tsuboi Hiroto、Goto Daisuke、Matsumoto Isao、Shibayama Shiro、Sumida Takayuki
    • Journal Title

      International Journal of Rheumatic Diseases

      Volume: 21 Issue: 12 Pages: 2071-2078

    • DOI

      10.1111/1756-185x.13381

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation.2018

    • Author(s)
      Nakamura Y, Matsuzaka T, Tahara-Hanaoka S, Shibuya K, Shimano H, Nakahashi-Oda C, Shibuya A.
    • Journal Title

      Cell Death Dis.

      Volume: 9(12) Issue: 12 Pages: 1181-1181

    • DOI

      10.1038/s41419-018-1226-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Allergin-1 on mast cells suppresses house dust mite-induced airway hyperresponsiveness in mice2018

    • Author(s)
      Hitomi K, Tahara-Hanaoka S, Miki H, Iwata K, Shibayama S, Kubo M, Shibuya A
    • Journal Title

      Int Immunol

      Volume: 30(9) Issue: 9 Pages: 429-434

    • DOI

      10.1093/intimm/dxy025

    • NAID

      120007133761

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cutting Edge: Identification of Marginal Reticular Cells as Phagocytes of Apoptotic B Cells in Germinal Centers2018

    • Author(s)
      Sato Kazuki、Honda Shin-ichiro、Shibuya Akira、Shibuya Kazuko
    • Journal Title

      The Journal of Immunology

      Volume: 200 Issue: 11 Pages: 3691-3696

    • DOI

      10.4049/jimmunol.1701293

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term survival of the mouse ES cell-derived mast cell, MEDMC-BRC6, in mast cell-deficient KitW-sh/W-sh mice2017

    • Author(s)
      Shibagaki Shohei、Tahara-Hanaoka Satoko、Hiroyama Takashi、Nakamura Yukio、Shibuya Akira
    • Journal Title

      International Immunology

      Volume: 29 Issue: 5 Pages: 235-242

    • DOI

      10.1093/intimm/dxx022

    • NAID

      120007134419

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Allergin-1 immunoreceptor suppresses house dust mite-induced allergic Th2 responses2018

    • Author(s)
      28.田原 聡子、三木 春香、人見 香織、Almeida Mariana、柴垣 翔平、金丸 和正、岩田 佳奈子、柴山 史朗、住田 孝之、渋谷 和子、渋谷 彰
    • Organizer
      第83回日本インターフェロン・サイトカイン学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhibition of house dust mite-induced Th2 responses by Allergin-1 immunoreceptor on dendritic cells.2017

    • Author(s)
      Tahara-Hanaoka S, Miki H, Hitomi K, Almeida MS, Iwata K, Kanemaru K, Shibayama S, Kubo M, Sumida T, Shibuya A
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inhibition of house dust mite-induced Th2 responses by Allergin-1 immunoreceptor on dendritic cells.2017

    • Author(s)
      Tahara-Hanaoka S, Miki H, Hitomi K, Almeida MS, Iwata K, Kanemaru K, Shibayama S, Kubo M, Sumida T, Shibuya A
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 筑波大学 免疫学研究室

    • URL

      http://immuno-tsukuba.com/index.html

    • Related Report
      2019 Annual Research Report 2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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