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Analysis of molecular mechanisms of intestinal homeostasis regulated by epithelial cells

Research Project

Project/Area Number 18K07174
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionOsaka University

Principal Investigator

KOHYAMA Masako  大阪大学, 感染症総合教育研究拠点, 准教授 (70311339)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腸管免疫 / 上皮細胞 / 腸内細菌
Outline of Final Research Achievements

The expression of MHC II molecules in intestinal epithelial cells and the expression of CD74 molecules that regulate MHC II molecules functions in intestinal epithelial cells are altered by different types of intestinal bacteria, and CD74 deficient mice show increased susceptibility to intestinal damage (irradiation-induced intestinal damage model and DSS-induced intestinal inflammation model). Furthermore, we generated mice lacking CD74 molecules specifically in small intestinal epithelial cells and analyzed the role of CD74 molecules in intestinal damage. The results revealed that CD74 molecules expressed on the cell surface of small intestinal epithelial cells play an important role in intestinal damage.

Academic Significance and Societal Importance of the Research Achievements

近年、腸内フローラとアレルギーや自己免疫疾患の関係が指摘され、その作用機序の解明に注目が集まっている。本研究では腸内細菌叢の変化によってその発現が制御される分子を同定し、腸管ダメージにおける役割の重要性を示した。この結果はこの分子をターゲットとした治療や、新薬開発につながるものと考えられる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses2022

    • Author(s)
      Kohyama Masako、Suzuki Tatsuya、Nakai Wataru、Ono Chikako、Matsuoka Sumiko、Iwatani Koichi、Liu Yafei、Sakai Yusuke、Nakagawa Atsushi、Tomii Keisuke、Ohmura Koichiro、Okada Masato、Matsuura Yoshiharu、Ohshima Shiro、Maeda Yusuke、Okamoto Toru、Arase Hisashi
    • Journal Title

      International Immunology

      Volume: 35 Issue: 1 Pages: 43-52

    • DOI

      10.1093/intimm/dxac044

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies2021

    • Author(s)
      Liu Y, Ohshima S, Arase H, et al.
    • Journal Title

      Cell

      Volume: Jun 24;184(13) Issue: 13 Pages: 3452-3466

    • DOI

      10.1016/j.cell.2021.05.032

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasmodium falciparum RIFIN is a novel ligand for inhibitory immune receptor LILRB2.2021

    • Author(s)
      Sakoguchi A, Saito F, Hirayasu K, Shida K, Matsuoka S, Itagaki S, Nakai W, Kohyama M, Suenaga T, Iwanaga S, Horii T, Arase H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 548 Pages: 167-173

    • DOI

      10.1016/j.bbrc.2021.02.033

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ウイルス感染による免疫応答とサイトカインストーム2021

    • Author(s)
      香山 雅子、荒瀬 尚
    • Journal Title

      実験医学

      Volume: 39 Pages: 524-529

    • Related Report
      2020 Research-status Report
  • [Journal Article] A TCR-like antibody against a proinsulin-containing fusion peptide ameliorates type 1 diabetes in NOD mice2020

    • Author(s)
      Matsumoto Y, Kishida K, Matsumoto M, Matsuoka S, Kohyama M, Suenaga T, Arase H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 534 Pages: 680-686

    • DOI

      10.1016/j.bbrc.2020.11.019

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex.2019

    • Author(s)
      Soodgupta D, White LS, Yang W, Johnston R, Andrews JM, Kohyama M, Murphy KM, Mosammaparast N, Payton JE, Bednarski JJ.
    • Journal Title

      Cell Rep.

      Volume: 29 Issue: 4 Pages: 829-843.e5

    • DOI

      10.1016/j.celrep.2019.09.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transport of cellular misfolded proteins to the cell surface by HLA-B27 free heavy chain.2019

    • Author(s)
      Yorifuji H, Arase N, Kohyama M, Hirano T, Suenaga T, Kumanogoh A, Arase H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 511 Issue: 4 Pages: 862-868

    • DOI

      10.1016/j.bbrc.2019.02.120

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FcγRIIIA-mediated activation of NK cells by IgG heavy chain complexed with MHC class II molecules.2019

    • Author(s)
      Shimizu Y, Kohyama M, Yorifuji H, Jin H, Arase N, Suenaga T, Arase H.
    • Journal Title

      Int Immunol.

      Volume: Epub ahead of print Issue: 5 Pages: 303-314

    • DOI

      10.1093/intimm/dxz010

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Invariant chain p41 mediates production of soluble MHC class II molecules.2019

    • Author(s)
      Shishido T, Kohyama M, Nakai W, Matsumoto M, Miyata H, Suenaga T, Arase H.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 509 Issue: 1 Pages: 216-221

    • DOI

      10.1016/j.bbrc.2018.12.106

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.2018

    • Author(s)
      Kayama H, Kohyama M, Okuzaki D, Motooka D, Barman S, Okumura R, Muneta M, Hoshino K, Sasaki I, Ise W, Matsuno H, Nishimura J, Kurosaki T, Nakamura S, Arase H, Kaisho T, Takeda K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 115 Issue: 33 Pages: 8418-8423

    • DOI

      10.1073/pnas.1808426115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 脾臓や肝臓の組織マクロファージとその分化制御機構2018

    • Author(s)
      香山雅子
    • Journal Title

      炎症と免疫

      Volume: 26 Pages: 192-196

    • Related Report
      2018 Research-status Report
  • [Presentation] SARS-CoV-2 ORF8 is a viral cytokine involved in lung inflammation2021

    • Author(s)
      Masako Kohyama, Tatsuya Suzuki, Toru Okamoto, Hisashi Arase
    • Organizer
      日本免疫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Immune activating receptors specific to Plasmodium falciparum-infected red blood cells2020

    • Author(s)
      AkihitoSakoguchi, Fumiji Saito, Kouyuki Hirayasu, Masako Kohyama, Shiroh Iwanaga, Toshihiro Horii, Hisashi Arase
    • Organizer
      第13回寄生虫感染免疫研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] FcγRIIIA-mediated activation of NK cells by IgG heavy chain complexed with MHC class II molecules2019

    • Author(s)
      Tadahiro Suenaga, Yuta Shimizu, Masako Kohyama, Hideki Yorifuji, Jin Hui, Noriko Arase, Hisashi Arase
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] CD74 isoform p41 regulates soluble MHC class II production2019

    • Author(s)
      Masako Kohyama, Sumiko Matsuoka, Tatsuya Shishido, Yuta Shimizu, Hisashi Arase
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] TSHR / MHC class II complexes are involved in the pathogenesis of Graves' disease2019

    • Author(s)
      Hui Jin, Noriko Arase, Masako Kohyama, Tadahiro Suenaga, Takehiko Sasazuki, Hisashi Arase
    • Organizer
      第18回あわじ感染と免疫フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] RIFINs of Plasmodium falciparum target multiple inhibitory receptors for immune evasion2019

    • Author(s)
      Akihito Sakoguchi, Fumiji Saito, Kouyuki Hirayasu, Kyoko Shida, Masako Kohyama, Tadahiro Suenaga, Shiroh Iwanaga, Hisashi Arase
    • Organizer
      第18回あわじ感染と免疫フォーラム
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] MHCクラスⅡ分子によるDNAの提示2019

    • Author(s)
      辻 英輝、大村 浩一郎、荒瀬 規子、香山 雅子、榊原 修平、菊谷 仁、末永 忠広、三森 経世、荒瀬 尚
    • Organizer
      第29 回Kyoto T cell Conference
    • Related Report
      2019 Research-status Report
  • [Presentation] T細胞レセプターと同様な抗原特異性を示す抗体による新たな免疫制御機構2018

    • Author(s)
      岸田 一輝, 香山雅子, 末永忠広, 荒瀬 尚
    • Organizer
      第28 回Kyoto T cell Conference
    • Related Report
      2018 Research-status Report
  • [Presentation] Host Molecules Associating with Human Herpesvirus 6(HHV-6)2018

    • Author(s)
      Yuriko Muramatsu, Tadahiro Suenaga, Masako Kohyama, Hisashi Arase
    • Organizer
      第17回あわじしま感染症・免疫フォーラム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] HLA-B27による細胞内ミスフォールド蛋白質輸送能2018

    • Author(s)
      依藤 秀樹, 荒瀬 規子, 平野 亨, 香山 雅子, 末永 忠広, 熊ノ郷 淳, 荒瀬 尚
    • Organizer
      第5回 JCRベーシックリサーチカンファレンス
    • Related Report
      2018 Research-status Report
  • [Presentation] Recognition of DNA / HLA-class II complex by anti-DNA antibodies from SLE patients2018

    • Author(s)
      Hideaki Tsuji, Koichiro Ohmura, Shuhei Sakakibara, Noriko Arase, Masako Kohyama, Tadahiro Suenaga, Hitodhi Kikutani, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] TSHR-stimulating autoantibody production by TSHR / MHC class II complexes2018

    • Author(s)
      Hui Jin, Noriko Arase, Masako Kohyama, TadahiroSuenaga, TakehikoSasazuki, HisashiArase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of T cell response by TCR-like antibodies2018

    • Author(s)
      Kazuki Kishida, Masako Kohyama,Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Deletion of iinvariant chain in adult mice resulted in autoantibody production2018

    • Author(s)
      Tatsuya Shishido, Masako Kohyama,Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of diabetogenic T cell response by antibodies against peptide-MHC class II complex2018

    • Author(s)
      Yushi Matsumoto, Kazuki Kishida, Sumiko Matsuoka, Masako Koyama, Tadahiro Suenaga, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] RIFINs of Plasmodium falciparum target multiple inhibitory receptors for immune evasion2018

    • Author(s)
      Akihito Sakoguchi, Fumiji Saito, Kouyuki Hirayasu, Kyoko Shida, Masako Kohyama, TadahiroSuenaga, Shiroh Iwanaga, Toshihiro Horii, Hisashi Arase
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] 免疫化学分野ホームページ

    • URL

      http://immchem.biken.osaka-u.ac.jp

    • Related Report
      2020 Research-status Report 2019 Research-status Report 2018 Research-status Report
  • [Patent(Industrial Property Rights)] 可溶型MHCクラスⅡ分子の産生誘導組成物、可溶型MHCクラスⅡ分子の産生誘導キット、可溶型MHCクラスⅡ分子の産生細胞、可溶型MHCクラスⅡ分子の産生細胞の製造方法および可溶型MHCクラスⅡ分子の製造方法2018

    • Inventor(s)
      荒瀬 尚、伊勢 雅子、宍戸 達也
    • Industrial Property Rights Holder
      荒瀬 尚、伊勢 雅子、宍戸 達也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-228986
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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