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Understanding the Ahr signal for the maintainance of intestinal epithelial cells

Research Project

Project/Area Number 21H02905
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKeio University

Principal Investigator

Ogata Haruhiko  慶應義塾大学, 医学部(信濃町), 教授 (30177117)

Co-Investigator(Kenkyū-buntansha) 筋野 智久  慶應義塾大学, 医学部(信濃町), 講師 (40464862)
細江 直樹  慶應義塾大学, 医学部(信濃町), 准教授 (90317131)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2023: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords潰瘍性大腸炎 / 炎症性腸疾患 / 大腸炎 / 小腸疾患
Outline of Research at the Start

炎症性腸疾患は炎症による組織破壊と組織修復、再生過程のアンバランスにより起きる疾患である。これまでの免疫を抑制する薬剤は炎症を抑制することで2次的に組織破壊を止めることで修復を促すことで治療を行ってきた。一方で近年使用されているAhr-ligandを中心とした生薬などはこれまでとは異なる過程である組織修復を増強することで炎症を抑制する可能性が期待されている。そこで内視鏡学的にCAD画像解析システムを併用し治癒過程を解析するとともに、その過程を時空間的な解析を含め免疫学的な手法を取り入れることで統合的に理解し、炎症性腸疾患の治療法の確立を検証する。

Outline of Final Research Achievements

Inflammatory bowel disease is characterized by destruction of the intestinal epithelium, and previous studies have revealed that immune regulatory mechanisms mediated by Tregs are important for intestinal epithelial protection. While the molecular mechanisms have been elucidated, the localization and dynamics of Tregs in the gastrointestinal tract have remained unclear for many years, and the mechanism by which Ahr signaling regenerates the intestinal epithelium via Tregs, which are inflammatory suppressor cells, has been elucidated. We have also developed an efficient endoscopic system by using machine learning in endoscopic examinations for inflammatory bowel disease.

Academic Significance and Societal Importance of the Research Achievements

これまで明らかでなかったAhr含有物質が腸管のホメオスタシス維持に重要であるというエビデンスに対して、本研究を通じて炎症性腸疾患モデルを抑制することで、その詳細なメカニズムを明らかとした。さらに1細胞の腸管内における局在解析を確立した。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (13 results)

All 2023 2022 2021

All Journal Article (13 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 9 results)

  • [Journal Article] Artificial intelligence quantifying endoscopic severity of ulcerative colitis in gradation scale2023

    • Author(s)
      Takabayashi Kaoru、Kobayashi Taku、...、Kanai Takanori、Ogata Haruhiko
    • Journal Title

      Digestive Endoscopy

      Volume: 1 Issue: 5 Pages: 1-10

    • DOI

      10.1111/den.14677

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development2023

    • Author(s)
      Ono Keiko、Sujino Tomohisa、Miyamoto Kentaro、Harada Yosuke、Kojo Satoshi、Yoshimatsu Yusuke、Tanemoto Shun、Koda Yuzo、Zheng Jiawen、Sayama Kazutoshi、Koide Tsuyoshi、...、Mucida Daniel、Taniuchi Ichiro、Kanai Takanori
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41467-023-40950-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease2023

    • Author(s)
      Umeda Satoko、 Sujino Tomohisa、、、Shiomi Daisuke、Ashida Hiroshi、Kanai Takanori
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 16 Issue: 6 Pages: 1011-1031

    • DOI

      10.1016/j.jcmgh.2023.08.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characteristics of flat‐type ulcerative colitis‐associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying2023

    • Author(s)
      Takabayashi Kaoru、Sugimoto Shinya、...、Ogata Haruhiko、Iwao Yasushi、Kanai Takanori
    • Journal Title

      Digestive Endoscopy

      Volume: 36 Issue: 4 Pages: 446-454

    • DOI

      10.1111/den.14628

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Enteropathy Associated with <i>Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1)</i> with Positive Immunohistochemistry for SLCO2A1 Protein2022

    • Author(s)
      Ariake Chizuru、Hosoe Naoki、Sakurai Hinako、Tojo Anna、Hayashi Yukie、JL Limpias Kamiya Kenji、Sujino Tomohisa、Takabayashi Kaoru、Kosaki Kenjiro、Seki Satowa、Hisamatsu Tadakazu、Ogata Haruhiko、Kanai Takanori
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 17 Pages: 2607-2611

    • DOI

      10.2169/internalmedicine.8939-21

    • NAID

      130008161632

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-09-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single-cell transcriptomics of human gut T cells identifies cytotoxic CD4+CD8A+ T cells related to mouse CD4 cytotoxic T cells2022

    • Author(s)
      Tanemoto Shun,Sujino Tomohisa,Miyamoto Kentaro,Moody Jonathan,Yoshimatsu Yusuke,Ando Yoshinari,Koya Ikuko,Harada Yosuke,Tojo Anna Okuzawa,Ono Keiko,Hayashi Yukie,Takabayashi Kaoru,Okabayashi Koji,Teratani Toshiaki,Mikami Yohei,Nakamoto Nobuhiro,Hosoe Naoki,Ogata Haruhiko,Hon Chung-Chau,Shin Jay W,Kanai Takanori
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 977117-977117

    • DOI

      10.3389/fimmu.2022.977117

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aryl hydrocarbon receptor signals in epithelial cells govern the recruitment and location of Helios+ Tregs in the gut2022

    • Author(s)
      Yoshimatsu Yusuke、Sujino Tomohisa、Hosoe Naoki、et al.
    • Journal Title

      Cell Reports

      Volume: 39 Issue: 6 Pages: 110773-110773

    • DOI

      10.1016/j.celrep.2022.110773

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes2022

    • Author(s)
      Harada Y, Sujino T, Miyamoto K, Nomura E, Yoshimatsu Y, Tanemoto S, Umeda S, Ono K, Mikami Y, Nakamoto N, Takabayashi K, Hosoe N, Ogata H, Ikenoue T, Hirao A, Kubota Y, Kanai T.
    • Journal Title

      iScience

      Volume: 25 Issue: 4 Pages: 104021-104021

    • DOI

      10.1016/j.isci.2022.104021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Feasibility and Safety of Endoscopic Ischemic Polypectomy and Clinical Outcomes in Patients with Peutz?Jeghers Syndrome (with Video)2022

    • Author(s)
      Limpias Kamiya Kenji J. L.、Hosoe Naoki、Takabayashi Kaoru、Okuzawa Anna、Sakurai Hinako、Hayashi Yukie、Miyanaga Ryoichi、Sujino Tomohisa、Ogata Haruhiko、Kanai Takanori
    • Journal Title

      Digestive Diseases and Sciences

      Volume: - Issue: 1 Pages: 252-258

    • DOI

      10.1007/s10620-022-07477-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advanced endoscopy for the management of inflammatory digestive diseases: Review of the Japan Gastroenterological Endoscopy Society core session2022

    • Author(s)
      Matsuura Minoru、Matsumoto Takayuki、Naito Yuji、Saitoh Yusuke、Kanai Takanori、Suzuki Yasuo、Tanaka Shinji、Ogata Haruhiko、Hisamatsu Tadakazu
    • Journal Title

      Digestive Endoscopy

      Volume: - Issue: 4 Pages: 729-735

    • DOI

      10.1111/den.14234

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential benefits of immunomodulator use with vedolizumab for maintenance of remission in ulcerative colitis2022

    • Author(s)
      Naganuma Makoto, Watanabe Kenji, Motoya Satoshi, Ogata Haruhiko, Matsui Toshiyuki, Suzuki Yasuo, ursos Lyann, Sakamoto Shigeru, Shikamura Mitsuhiro, Hori Tetsuharu, Frenandez Jovelle, Watanabe Mamoru, Hibi Toshifumi, Kanai Takanori
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 1 Issue: 1 Pages: 81-88

    • DOI

      10.1111/jgh.15667

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Video capsule endoscopy in inflammatory bowel disease.2021

    • Author(s)
      Limpias Kamiya KJL, Hosoe N, Hayashi Y, Kawaguchi T, Takabayashi K, Ogata H, Kanai T
    • Journal Title

      DEN open

      Volume: 16 Issue: 1

    • DOI

      10.1002/deo2.26

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Underwater endoscopic mucosal resection for a sporadic adenoma located at severe longitudinal ulcer scars in ulcerative colitis.2021

    • Author(s)
      Takabayashi K, Kato M, Sasaki M, Iwao Y, Ogata H, Kanai T, Yahagi N.
    • Journal Title

      Endoscopy

      Volume: - Issue: 01 Pages: E30-E31

    • DOI

      10.1055/a-1368-3796

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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