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Analysis of Gastric Carcinogenesis Mechanisms Focusing on TLR10 Diversity

Research Project

Project/Area Number 20K08824
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionSapporo Medical University

Principal Investigator

Nagashima Hiroyuki  札幌医科大学, 医学部, 研究員 (90592840)

Co-Investigator(Kenkyū-buntansha) 山本 聡  札幌医科大学, 医学部, 助教 (10588479)
加藤 淳二  札幌医科大学, 医学部, 教授 (20244345)
白石 宗  札幌医科大学, 医学部, 助教 (70725168)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsToll like receptor / LPS / Helicobacter pylori / Anti-inflammatory / toll like receptor 10 / H. pylori LPS / 常在菌 / 胃がん / TLR10 / 腸内細菌 / Lipid A / ピロリ菌 / toll-like receptor 10 / 自然免疫 / Lipopolysaccharide
Outline of Research at the Start

申請者のこれまでの研究によってH. pylori感染の疫学調査をする中でTLR10が炎症反応の違いを生み出し、胃がん発生に関与している可能性を示唆する結果を得た。
本研究ではTLR10のリガンドの同定、胃がん発症リスクアレルを同定し、H. pylori はTLR10によってどのように認識され宿主免疫応答を誘導し、慢性炎症や胃がんの発生に寄与するのかについて解析を行う

Outline of Final Research Achievements

We have focused on the structure of Helicobacter pylori (H. pylori) LPS and reported that it is recognized by Toll like receptor 10 (TLR10), and demonstrated that TLR10 influences gastric cancer development and the degree of gastritis in H. pylori infection. We have also demonstrated that, unlike other TLRs, signals from TLR10 show an anti inflammatory response, and that similar responses are observed in Bacteroides, Akkaremansia, and other genera in addition to the LPS of H. pylori.

Academic Significance and Societal Importance of the Research Achievements

LPSは菌の種類によって多様な形態をとるが、常在菌におけるLPSに共通の構造がTLR10に認識されている可能性を示唆する結果を得た。これまでの不明とされていたTLR10のリガンドは、実は体内に多量に存在しており、その免疫反応もAnti-inflammatoryな反応が中心であった。学術的な意義としては今後IBSやirAE腸炎などの治療薬の開発につながる可能性を示唆する結果と考えている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2024

All Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] PERCENTAGE OF BACTEROIDES SPEICIES IN MICROBIOME AFFECT THERAPEUTIC EFFICACY OF IMMUNE CHECKPOINT INHIBITORS FOR HEPATOCELLULAR CARCINOMA.2024

    • Author(s)
      Hiroyuki Nagashima, Masahiro HIrakawa, Tamotsu Sagawa
    • Organizer
      DDW2014 Washinton D.C.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2025-01-30  

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