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Mechanism of intestinal midrobiota regulation by intestinal IgA

Research Project

Project/Area Number 15H04732
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionThe University of Tokyo (2017)
Nara Institute of Science and Technology (2016)
Nagahama Institute of Bio-Science and Technology (2015)

Principal Investigator

Shinkura Reiko  東京大学, 分子細胞生物学研究所, 教授 (50362471)

Co-Investigator(Renkei-kenkyūsha) KUROKAWA Ken  国立遺伝学研究所, 生命情報研究センター, 教授 (20343246)
MORI Hiroshi  国立遺伝学研究所, 生命情報研究センター, 助教 (40610837)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords粘膜免疫 / 抗体 / 腸内細菌 / 腸内細菌叢 / IgA抗体 / 腸管免疫
Outline of Final Research Achievements

Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defense against pathogens and in the maintenance of intestinal homeostasis through gut microbial control. Our main question is what kind of bacterial molecule intestinal high-affinity IgA recognizes and targets. To address this question, we generated hybridomas from IgA producing cells in the small intestine of wild type mice. We selected W27 IgA that binds to multiple bacteria but not beneficial ones such as Lactobacillus casei. Via specific recognition of an epitope in serine hydroxymethyltransferase (SHMT), a bacterial metabolic enzyme, W27 IgA selectively inhibited the in vitro growth of Escherichia coli (E. coli), while having no effect on unbound beneficial bacteria such as L. casei. It indicates that W27 IgA has an ability to improve the intestinal environment.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results,  Open Access: 4 results) Presentation (16 results) (of which Int'l Joint Research: 6 results,  Invited: 9 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Fudan University(China)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 腸管IgA抗体による腸内細菌制御機構2018

    • Author(s)
      新藏礼子
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 46-50

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Intestinal IgA as a modulator of the gut microbiota.2017

    • Author(s)
      Okai S, Usui F, Ohta M, Mori H, Kurokawa K, Matsumoto S, Kato T, Miyauchi E, Ohno H, Shinkura R.
    • Journal Title

      Gut Microbes

      Volume: - Issue: 5 Pages: 1-7

    • DOI

      10.1080/19490976.2017.1310357

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Decreased Taxon-Specific IgA Response in Relation to the Changes of Gut Microbiota Composition in the Elderly2017

    • Author(s)
      Sugahara Hirosuke、Okai Shinsaku、Odamaki Toshitaka、Wong Chyn B.、Kato Kumiko、Mitsuyama Eri、Xiao Jin-Zhong、Shinkura Reiko
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 1-8

    • DOI

      10.3389/fmicb.2017.01757

    • NAID

      120006354237

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accelerated Systemic Autoimmunity in the Absence of Somatic Hypermutation in 564Igi: A Mouse Model of Systemic Lupus with Knocked-In Heavy and Light Chain Genes2017

    • Author(s)
      McDonald Gabrielle、Medina Carlos O.、Pilichowska Monika、Kearney John F.、Shinkura Reiko、Selsing Erik、Wortis Henry H.、Honjo Tasuku、Imanishi-Kari Thereza
    • Journal Title

      Frontiers in Immunology

      Volume: 8 Pages: 1-15

    • DOI

      10.3389/fimmu.2017.01094

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 腸管IgA抗体による腸内細菌及び炎症性疾患の制御機構2017

    • Author(s)
      岡井晋作、新藏礼子
    • Journal Title

      感染・炎症・免疫

      Volume: 47 Pages: 73-75

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 腸管IgA抗体による腸内細菌制御のメカニズム-IgA抗体は腸管内でなにをしている?2017

    • Author(s)
      臼井文人、新藏礼子
    • Journal Title

      化学と生物

      Volume: 55 Pages: 596-601

    • NAID

      130007437196

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 悪玉腸内細菌増殖を抑えるIgA抗体2017

    • Author(s)
      新藏礼子、岡井晋作、臼井文人
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 75 Pages: 142-143

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 腸管IgA抗体による腸内細菌制御2017

    • Author(s)
      岡井晋作,新藏礼子
    • Journal Title

      実験医学

      Volume: 42 Pages: 42-47

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 腸内常在細菌に対するモノクローナルIgAの応答2017

    • Author(s)
      新藏礼子
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 67 Pages: 612-616

    • Related Report
      2017 Annual Research Report
  • [Journal Article] High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice.2016

    • Author(s)
      Okai S, Usui F, Yokota S, Hori-I Y, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R.
    • Journal Title

      Nature Microbiology

      Volume: 1 Issue: 9 Pages: 16103-16103

    • DOI

      10.1038/nmicrobiol.2016.103

    • NAID

      120005818448

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高親和性モノクローナルIgAはマウスの腸内細菌叢を改善し大腸炎を予防する2016

    • Author(s)
      岡井晋作、新藏礼子
    • Journal Title

      実験医学

      Volume: 34(19) Pages: 3185-3188

    • Related Report
      2016 Annual Research Report
  • [Journal Article] ’’微生物と人類の共存’’をゲノムの視点から2016

    • Author(s)
      新藏礼子、他共著
    • Journal Title

      生物の科学

      Volume: 71(1) Pages: 77-85

    • Related Report
      2016 Annual Research Report
  • [Journal Article] IgA抗体による腸内細菌の制御機構2015

    • Author(s)
      新藏 礼子
    • Journal Title

      医学のあゆみ

      Volume: 増刊号 Pages: 375-380

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Presentation] 腸内細菌叢改善のためのIgA抗体医薬2018

    • Author(s)
      新藏 礼子
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腸管IgA抗体による常在腸内細菌制御機構の解明と応用2018

    • Author(s)
      新藏 礼子
    • Organizer
      千里ライフサイエンスセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Intestinal IgA as a modulator of the gut microbiota2017

    • Author(s)
      Reiko Shinkura
    • Organizer
      ゲノム先進シンポジウム
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2017-01-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸管IgA抗体による常在腸内細菌叢制御2017

    • Author(s)
      新藏 礼子
    • Organizer
      第27回 日本サイトメトリー学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腸管IgA抗体による腸内細菌制御2017

    • Author(s)
      新藏 礼子
    • Organizer
      第35回サイトプロテクション研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] High-affinity intestinal IgA as a modulator of the gut microbiota.2017

    • Author(s)
      Reiko Shinkura
    • Organizer
      Cytokine 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Intestinal IgA as a modulator of the gut microbiota2017

    • Author(s)
      Reiko Shinkura
    • Organizer
      1st International Seminar on Biotechnology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Intestinal IgA as a modulator of the gut microbiota.2017

    • Author(s)
      Reiko Shinkura
    • Organizer
      The 16th Awaji International Forum on Infection and Immunity
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel compounds that induce selective class switching to IgA2017

    • Author(s)
      Hitomi Sakatani, Kota Yamamoto, et al.
    • Organizer
      The 46th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2017 Annual Research Report
  • [Presentation] Monoclonal intestinal IgAs are poly-reactive but recognize a specific amino acid sequence of protein expressed by multiple bacteria2016

    • Author(s)
      Fumihito Usui
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High-affinity, poly-reactive IgA is required for gut homeostatic maintenance to prevent colitis in mice2016

    • Author(s)
      Shinsaku Okai
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腸管IgA抗体は多種類の腸内細菌の特異的なアミノ酸配列を認識している。2015

    • Author(s)
      臼井 文人、新藏 礼子、他
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腸炎モデルマウスに対する腸管IgA抗体の作用機序の解明2015

    • Author(s)
      岡井 晋作、新藏 礼子、他
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] High-affinity, poly-reactive IgA is required for gut homeostatic maintenance to prevent colitis in mice.2015

    • Author(s)
      岡井 晋作、新藏 礼子、他
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Monoclonal intestinal IgAs are poly-reactive but recognize a specific amino acid sequence of protein expressed by multiple bacteria.2015

    • Author(s)
      臼井 文人、新藏 礼子、他
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] IgA抗体による腸内細菌制御ー炎症性腸疾患新規治療薬候補としてー2015

    • Author(s)
      新藏 礼子
    • Organizer
      第8回鹿児島FD・IBS研究会
    • Place of Presentation
      鹿児島大学
    • Year and Date
      2015-07-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 応用免疫学(新藏研究室)

    • URL

      http://bsw3.naist.jp/shinkura/

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチド2015

    • Inventor(s)
      新藏礼子、岡井晋作、臼井文人
    • Industrial Property Rights Holder
      新藏礼子、岡井晋作、臼井文人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-06-11
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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