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Elucidation of T-independent IgA class switch machinery

Research Project

Project/Area Number 17H04089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKeio University

Principal Investigator

Hase Koji  慶應義塾大学, 薬学部(芝共立), 教授 (20359714)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
KeywordsIgA抗体 / 腸内細菌 / 酪酸 / IgA / 粘膜免疫 / 短鎖脂肪酸 / 腸管免疫 / 免疫学 / 細胞・組織 / 細菌
Outline of Final Research Achievements

Secretory immunoglobulin A, the most abundant antibody isotype in the body, maintains a mutual relationship with commensal bacteria and acts as a primary barrier at the mucosal surface. Colonization by commensal bacteria induces an IgA response, at least partly through a T-cell-independent process. However, the mechanism underlying the commensal-bacteria-induced T-cell-independent IgA response has yet to be fully clarified. Here, we show that commensal-bacteria-derived butyrate promotes T-cell-independent IgA class switching recombination (CSR) in the mouse colon.

Academic Significance and Societal Importance of the Research Achievements

近年、腸内共生バランス失調(ディスバイオーシス)が炎症性腸疾患、自己免疫性疾患、動脈硬化、がん、糖尿病、肝硬変などの発症と関連するとの報告が相次いでいる。分泌型IgAは腸内細菌のバランス制御にも関わっており、分泌型IgAの質と量を適切に保つことは、ディスバイオーシスの防止に重要である。よって、本研究で行った分泌型IgA抗体の産生機構の解明は、腸内環境の改善を標的とした新たな医療の発展に繋がるものと期待できる。

Report

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

    (27 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results)

  • [Int'l Joint Research] Max-Plank-Institute(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Max-Planck-Institute(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice2020

    • Author(s)
      Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, Aoki R, Isobe Y, Kashihara D, Inoue D, Inaba A, Takamura Y, Taira S, Kumaki S, Watanabe M, Ito M, Nakagawa F, Irie J, Kakuta H, Shinohara M, Iwatsuki K, Tsujimoto G, Ohno H, Arita M, Itoh H, Hase K.
    • Journal Title

      Science

      Volume: 367 Issue: 6481 Pages: 8429-8429

    • DOI

      10.1126/science.aaw8429

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteoprotegerin-dependent Mcell self-regulation balances gut infection and immunity.2020

    • Author(s)
      Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, KawakamiE, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, KaishoT, Iwanaga T, Hase K.
    • Journal Title

      Nat Commun

      Volume: 11 Issue: 1 Pages: 234-234

    • DOI

      10.1038/s41467-019-13883-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microfold cell-dependent antigen transport alleviates infectious colitis by inducing antigen-specific cellular immunity2020

    • Author(s)
      Nakamura Yutaka、Mimuro Hitomi、Kunisawa Jun、Furusawa Yukihiro、Takahashi Daisuke、Fujimura Yumiko、Kaisho Tsuneyasu、Kiyono Hiroshi、Hase Koji
    • Journal Title

      Mucosal Immunology

      Volume: in press Issue: 4 Pages: 679-690

    • DOI

      10.1038/s41385-020-0263-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon.2020

    • Author(s)
      Junya Isobe, Shintarou Maeda, Yuuki Obata, Keito Iizuka, Yutaka Nakamura, Yumiko Fujimura, Tatsuki Kimizuka, Kouya Hattori, Yun-Gi Kim, Tatsuya Morita, Ikuo Kimura, Stefan Offermanns, Takahiro Adachi, Atsuhito Nakao, Hiroshi Kiyono, Daisuke Takahashi, Koji Hase
    • Journal Title

      International Immunology

      Volume: 32 Issue: 4 Pages: 243-258

    • DOI

      10.1093/intimm/dxz078

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: Immunological Consequences of Antigen Sampling at Mucosal Surfaces2019

    • Author(s)
      Mabbott Neil A.、Hase Koji
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 2773-2773

    • DOI

      10.3389/fimmu.2019.02773

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Roles of Peyer's Patches and Microfold Cells in the Gut Immune System: Relevance to Autoimmune Diseases2019

    • Author(s)
      Kobayashi Nobuhide、Takahashi Daisuke、Takano Shunsuke、Kimura Shunsuke、Hase Koji
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 2345-2345

    • DOI

      10.3389/fimmu.2019.02345

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses2019

    • Author(s)
      Nagai M、Noguchi R、Takahashi D、Morikawa T、Koshida K、Komiyama S、Ishihara N、Yamada T、Kawamura YI.、Muroi K、Hattori K、Kobayashi N、Fujimura Y、Hirota M、Matsumoto R、Aoki R、Tamura-Nakano M、Sugiyama M、Katakai T、Sato S、Takubo K、Dohi T、Hase K
    • Journal Title

      Cell

      Volume: 178 Issue: 5 Pages: 1072-1087

    • DOI

      10.1016/j.cell.2019.07.047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis2019

    • Author(s)
      Yamada Takahiro、Hino Shingo、Iijima Hideki、Genda Tomomi、Aoki Ryo、Nagata Ryuji、Han Kyu-Ho、Hirota Masato、Kinashi Yusuke、Oguchi Hiroyuki、Suda Wataru、Furusawa Yukihiro、Fujimura Yumiko、Kunisawa Jun、Hattori Masahira、Fukushima Michihiro、Morita Tatsuya、Hase Koji
    • Journal Title

      EBioMedicine

      Volume: 48 Pages: 513-525

    • DOI

      10.1016/j.ebiom.2019.09.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier2019

    • Author(s)
      Zai Khadijah、Ishihara Narumi、Oguchi Hiroyuki、Hirota Masato、Kishimura Akihiro、Mori Takeshi、Hase Koji、Katayama Yoshiki
    • Journal Title

      Journal of Biomaterials Science, Polymer Edition

      Volume: 30 Issue: 1 Pages: 1-11

    • DOI

      10.1080/09205063.2018.1493671

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A partial agonist for retinoid X receptor mitigates experimental colitis2018

    • Author(s)
      Onuki Masayoshi、Watanabe Masaki、Ishihara Narumi、Suzuki Koichiro、Takizawa Kei、Hirota Masato、Yamada Takahiro、Egawa Aiko、Shibahara Osamu、Nishii Midori、Fujihara Michiko、Makishima Makoto、Takahashi Daisuke、Furusawa Yukihiro、Kakuta Hiroki、Hase Koji
    • Journal Title

      International Immunology

      Volume: 31 Issue: 4 Pages: 251-262

    • DOI

      10.1093/intimm/dxy089

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Administration of Porphyromonas gingivalis Alters the Gut Microbiome and Serum Metabolome2018

    • Author(s)
      Kato Tamotsu、Yamazaki Kyoko、Nakajima Mayuka、Date Yasuhiro、Kikuchi Jun、Hase Koji、Ohno Hiroshi、Yamazaki Kazuhisa
    • Journal Title

      mSphere

      Volume: 3 Issue: 5 Pages: 1-11

    • DOI

      10.1128/msphere.00460-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic effect of vitamin D3-containing nanostructured lipid carriers on inflammatory bowel disease2018

    • Author(s)
      Zai Khadijah、Hirota Masato、Yamada Takahiro、Ishihara Narumi、Mori Takeshi、Kishimura Akihiro、Suzuki Koichiro、Hase Koji、Katayama Yoshiki
    • Journal Title

      Journal of Controlled Release

      Volume: 286 Pages: 94-102

    • DOI

      10.1016/j.jconrel.2018.07.019

    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Intestinal Epithelial Cell-specific Deletion of α-Mannosidase II Ameliorates Experimental Colitis2018

    • Author(s)
      Suzuki K., Yamada T, Yamazaki K, Hirota M, Ishihara N, Sakamoto M, Takahashi D, Iijima H, Hase K.
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 1 Pages: 25-39

    • DOI

      10.1247/csf.17022

    • NAID

      130006513071

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage extracellular chromatin release induced by Mac-1 mediated platelet-macrophage interactions triggers acute kidney injury in rhabdomyolysis.2018

    • Author(s)
      Okubo K, Kurosawa M, Kamiya M, Urano Y, Suzuki A, Yamamoto K, Hase K, Homma K, Sasaki J, Miyauchi H, Hoshino T, Hayashi M, Mayadas TN, Hirahashi J.
    • Journal Title

      Nat. Med.

      Volume: 24 Issue: 2 Pages: 232-238

    • DOI

      10.1038/nm.4462

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.2017

    • Author(s)
      Jinnohara T, Kanaya T, Hase K, Sakakibara S, Kato T, Tachibana N, Sasaki T, Hashimoto Y, Sato T, Watarai H, Kunisawa J, Shibata N, Williams I, Kiyono H, and Ohno H.
    • Journal Title

      J. Exp. Med.

      Volume: 214 Issue: 6 Pages: 1607-1618

    • DOI

      10.1084/jem.20160770

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 栄養シグナルによる免疫バリアの制御2020

    • Author(s)
      長谷耕二
    • Organizer
      東邦大学研究ブランディング事業最終シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 栄養シグナルによるパイエル板リンパ球動態制御2019

    • Author(s)
      長谷耕二
    • Organizer
      30th Forum in DOJIN “Nutrio-Metabolomic Pathology”
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Nutritional signals regulate lymphocyte homing to gut-associated lymphoid tissue2019

    • Author(s)
      Koji Hase
    • Organizer
      The 7th International Conference on Food Factors (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 栄養シグナルによるパイエル板リンパ球動態制御2019

    • Author(s)
      長谷耕二
    • Organizer
      Science Pioneers Consortium (SPC) 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌を標的とした創薬イノベーション2019

    • Author(s)
      長谷耕二
    • Organizer
      JASIS2019ライフサイエンスイノベーション
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Nutritional Signals regulate lymphocyte homing to gut-associated lymphoid tissue2019

    • Author(s)
      Koji Hase
    • Organizer
      The 48th Annual Meeting of Japanese Society for Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 食物アレルギーの発症に及ぼす腸内代謝物の影響2019

    • Author(s)
      長谷耕二
    • Organizer
      第68回日本アレルギー学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 栄養シグナルによるパイエル板リンパ球動態制御2019

    • Author(s)
      長谷耕二
    • Organizer
      日本食品免疫学会設立15周年記念学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腸管における免疫監視機構2019

    • Author(s)
      長谷耕二
    • Organizer
      第22回 日本臨床腸内微生物学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Microbiota-derived metabolites shape mucosal barrier and immunity2017

    • Author(s)
      Koji Hase
    • Organizer
      Korean Society of Nephrology (KSN) 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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

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