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Analysis of Molecular Mechanisms for Modulation of Immune-Regulatory Function of Intestinal Epithelia by Food Factors

Research Project

Project/Area Number 21380077
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionThe University of Tokyo

Principal Investigator

TOTSUKA Mamoru  東京大学, 大学院・農学生命科学研究科, 准教授 (70227601)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2009: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords腸管上皮細胞 / Toll様受容体 / 腸管免疫系 / IgA / サイトカイン / プロバイオティクス / カルノシン / 乳酸菌 / ビフィズス菌 / 腸管免疫 / プロシアニジン
Research Abstract

Function of food factors that modulate immune-regulatory functions of intestinal epithelial cells(IEC) was analyzed. Carnosine enhanced the cytokine secretion from IEC stimulated with bacterial components. The supernatant of the IEC upregulated IgA production by B cells derived from mouse lamina propria. Oral administration of carnosine increased the amount of IgA in mucosa of the mouse small intestine. We also found that bifidobacteria upregulated the expression of a transcytotic carrier protein for IgA in IEC, that oral administration of lactobacilli induced regulatory T cells and enhanced oral tolerance induction, and that naringenin has the capacity to induce regulatory T cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (53 results)

All 2012 2011 2010 2009

All Journal Article (14 results) (of which Peer Reviewed: 13 results) Presentation (36 results) Book (3 results)

  • [Journal Article] Dietary flavonoid naringenin induces regulatory T cells via an aryl hydrocarbon receptor mediated pathway2012

    • Author(s)
      Hsi-Kai Wang, Chen-Hao Yeh, Taku Iwamoto, Hideo Satsu, Makoto Shimizu, Mamoru Totsuka
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: Vol.60(2) Issue: 9 Pages: 2172-2178

    • DOI

      10.1021/jf204625y

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of polymeric immunoglobulin receptor expression by the heat-inactivated potential probiotic Bifidobacterium bifidum OLB6378 in a mouse intestinal explant model2012

    • Author(s)
      Y.Nakamura
    • Journal Title

      Scand J Immunol

      Volume: 72 Issue: 2 Pages: 176-183

    • DOI

      10.1111/j.1365-3083.2011.02645.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lactobacillus gasseri OLL2809 and its RNA directly suppress proliferation of CD4+T cells through a MyD88-dependent signalling pathway2011

    • Author(s)
      Ayako Yoshida, Kiyoshi Yamada, Yasumasa Yamazaki, Toshihiro Sashihara, Shuji Ikegami, Makoto Shimizu, Mamoru Totsuka
    • Journal Title

      Immunology

      Volume: Vol.133(4) Issue: 4 Pages: 442-451

    • DOI

      10.1111/j.1365-2567.2011.03455.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of Intestinal Epithelial Cell Lines from Adult Mouse Small and Large Intestinal Crypts2011

    • Author(s)
      Taku Iwamoto, Kiyoshi Yamada, Makoto Shimizu, Mamoru Totsuka
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 75 Issue: 5 Pages: 925-929

    • DOI

      10.1271/bbb.100887

    • NAID

      10028272672

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Makoto Shimizu, Synergistic effect of Tumor Necrosis Factor-αand hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells2011

    • Author(s)
      HeeSun Shin, Zhaohui Zhao, Hideo Satsu, Mamoru Totsuka
    • Journal Title

      Inflammation

      Volume: Vol.34(5) Issue: 5 Pages: 440-447

    • DOI

      10.1007/s10753-010-9251-y

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of Tumor Necrosis Factor-α and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells2011

    • Author(s)
      HeeSun Shin, et al.
    • Journal Title

      Inflammation

      Volume: (掲載確定,掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IEX-1 suppressed apoptotic damage in human intestinal epithelial Caco-2 cells induced by coculturing with macrophage-like THP-1 cells.2011

    • Author(s)
      Yoko Ishimoto, et al.
    • Journal Title

      Bioscience Reports

      Volume: 31 Pages: 345-351

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of immunological functions of small and large epithelial cell lines established from adult mouse intestinal crypt2011

    • Author(s)
      Taku Iwamoto, et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: (掲載確定,掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient up-regulation of immunity- and apoptosis-related genes in Caco-2 cells cocultured with THP-1 cells evaluated by a DNA microarray analysis2010

    • Author(s)
      Yoko Ishimoto, et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 74巻2号

      Pages: 437-439

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transepithelial Transport of Macromolecular Substances in IL-4 Treated Human Intestinal T84 Cell Monolayers2009

    • Author(s)
      Tetsunosuke Mochizuki, Hideo Satsu, Mamoru Totsuka, and Makoto Shimizu
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 73 Issue: 11 Pages: 2422-2426

    • DOI

      10.1271/bbb.90383

    • NAID

      10027547657

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a Primary Culture Method for Mouse Intestinal Epithelial Cells by Organ Culture of Fetal Small Intestine2009

    • Author(s)
      Kiyoshi Yamada, Kanako Sato, Satoru Morishita, Shuichi Kaminogawa, and Mamoru Totsuka
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 73 Issue: 8 Pages: 1849-1855

    • DOI

      10.1271/bbb.90246

    • NAID

      10027544814

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a primary culture method for mouse intestinal epithelial cells by organ culture of fetal small intestine2009

    • Author(s)
      Kiyoshi Yamada, et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 73巻8号

      Pages: 1849-1855

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transepithelial transport of macromolecular substances in IL-4 treated human intestinal T84 cell monolayers2009

    • Author(s)
      Tetsunosuke Mochizuki, et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 73巻11号

      Pages: 2422-2426

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      戸塚護
    • Journal Title

      ミルクの事典(分担執筆:III.乳・乳製品と健康 4.2プレバイオティクス)(朝倉書店)

      Pages: 248-253

    • Related Report
      2009 Annual Research Report
  • [Presentation] 腸管上皮細胞のToll様受容体刺激を介した免疫調節機能に対するカルノシンの亢進効果2012

    • Author(s)
      津田悠一
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学(京都府)
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 柑橘類由来ナリンゲニンにより誘導されるマウス制御性T細胞の機能解析2012

    • Author(s)
      王璽凱
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学(京都府)
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 腸管上皮細胞のIgA輸送活性およびIgA産生誘導活性を増強する食品成分の評価2011

    • Author(s)
      戸塚護
    • Organizer
      日本動物細胞工学会2011年度大会
    • Place of Presentation
      東京大学山上会館(東京都)
    • Year and Date
      2011-07-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 腸管上皮細胞のIgA輸送活性およびIgA産生誘導活性を増強する食品成分の評価2011

    • Author(s)
      戸塚護
    • Organizer
      日本動物細胞工学会2011年度大会
    • Place of Presentation
      東京大学山上会館(東京都)(招待講演)
    • Year and Date
      2011-07-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Lactobacillus gasseri OLL2809投与による粘膜固有層における経口免疫寛容誘導の促進2011

    • Author(s)
      吉田綾子
    • Organizer
      第15回腸内細菌学会
    • Place of Presentation
      東京医科歯科大学M & Dタワー大講堂(東京都)
    • Year and Date
      2011-06-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Lactobacillus gasseri OLL2809投与による粘膜固有層における経口免疫寛容誘導の促進2011

    • Author(s)
      吉田綾子, 他
    • Organizer
      第15回腸内細菌学会
    • Place of Presentation
      東京医科歯科大学M&Dタワー大講堂(東京都)
    • Year and Date
      2011-06-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] IgA系粘膜免疫の食品因子による増強2011

    • Author(s)
      戸塚護
    • Organizer
      第11回日本抗加齢医学会総会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-05-28
    • Related Report
      2011 Final Research Report
  • [Presentation] IgA系粘膜免疫の食品因子による増強2011

    • Author(s)
      戸塚護
    • Organizer
      第11回日本抗加齢医学会総会
    • Place of Presentation
      国立京都国際会館(京都府)(招待講演)
    • Year and Date
      2011-05-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Screening and evaluation of dietary aryl hydrocarbon receptors(AhR) ligands inducing differentiation of regulatory T cells2011

    • Author(s)
      Wang, H-K
    • Organizer
      5th International Conference on Food Factors
    • Place of Presentation
      Taipei International Convention Center(台北、台湾)
    • Related Report
      2011 Final Research Report
  • [Presentation] 成体マウス由来小腸および大腸上皮細胞株の樹立と免疫機能解析2011

    • Author(s)
      岩本拓
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都女子大学(京都府)
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] カルノシンが腸管上皮細胞を介した粘膜固有層のIgA産生に与える作用の解析2011

    • Author(s)
      津田悠一, 他
    • Organizer
      第7回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学安田講堂(東京都)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Screening and evaluation of dietary aryl hydrocarbon receptors (AhR) ligands inducing differentiation of regulatory T cells2011

    • Author(s)
      Wang, H-K, et al.
    • Organizer
      5th International Conference on Food Factors
    • Place of Presentation
      Taipei International Convention Center(台北、台湾)
    • Related Report
      2011 Annual Research Report
  • [Presentation] マウス腸管上皮細胞のToll様受容体リガンド刺激で誘導されるサイトカイン産生に対する食品因子の増強作用2011

    • Author(s)
      津田悠一, 他
    • Organizer
      第6回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] プロバイオティック乳酸菌投与による経口免疫寛容の強化と粘膜固有層細胞への作用を介した制御性T細胞機能の増強2011

    • Author(s)
      吉田綾子, 他
    • Organizer
      第6回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] TLRリガンドにより誘導される腸管上皮サイトカイン産生に対するスフィンゴシン-1-リン酸の作用解析2011

    • Author(s)
      岩本拓, 他
    • Organizer
      第6回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of regulatory CD4^+ T cell subsets induced by oral administration of Lactobacillus gasseri OLL2809 in orally tolerized DO11.10 mice.2011

    • Author(s)
      吉田綾子, 他
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Comparative analysis of the expression of Toll-like receptors and cytokines in epithelial cell lines and ex vivo cells from mouse small and large intestines2011

    • Author(s)
      岩本拓, 他
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Lactobacillus gasseri OLL2809投与が腸管免疫系に与える影響2011

    • Author(s)
      吉田綾子, 他
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナリンゲニンによるマウスTh17細胞への分化誘導機構の解析2011

    • Author(s)
      ベ・ミンジョン, 他
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] Naringeninと食品由来AHRリガンドによるマウス制御性T細胞の誘導機能2011

    • Author(s)
      王璽凱, 他
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] カルノシンはTLRリガンド刺激した腸管上皮細胞によるIgA産生誘導因子の産生を増強する2011

    • Author(s)
      津田裕一, 他
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] クロロゲン酸及びコーヒー酸による抗炎症作用とその機構解析2011

    • Author(s)
      申喜淳, 他
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] マウス小腸および大腸由来上皮細胞株の菌体成分に対する応答の比較解析2010

    • Author(s)
      岩本拓
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2010-03-29
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Lactobacillus gasseri OLL2809生菌体の投与が経口免疫寛容誘導に与える影響2010

    • Author(s)
      吉田綾子, 他
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 酸化ストレスによる腸管上皮IL-8産生亢進に対するクロロゲン酸の抑制機構解析及び構造活性相関2010

    • Author(s)
      申喜淳, 他
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 腸管上皮細胞によるIgA輸送および産生誘導の食品由来因子による増強2010

    • Author(s)
      戸塚護
    • Organizer
      第3回日本食品免疫学会シンポジウム
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2010-01-18
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Analysis of regulatory CD4+T cell subsets induced by oral administration of Lactobacillus gasseri OLL2809 in orally tolerized DO11. 10 mice2010

    • Author(s)
      吉田綾子
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場(兵庫県)
    • Related Report
      2011 Final Research Report
  • [Presentation] Comparative analysis of the expression of Toll-like receptors and cytokines in epithelial cell lines and ex vivo cells from mouse small and large intestines2010

    • Author(s)
      岩本拓
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場(兵庫県)
    • Related Report
      2011 Final Research Report
  • [Presentation] マウス腸管上皮細胞のToll様受容体リガンド刺激で誘導されるサイトカイン産生に対する食品因子の増強作用2010

    • Author(s)
      津田悠一
    • Organizer
      第6回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2011 Final Research Report
  • [Presentation] Lactobacillus gasseri OLL2809の経口投与によるDO11. 10マウスの経口免疫寛容誘導の強化2009

    • Author(s)
      吉田綾子
    • Organizer
      日本免疫学会2009年度大会
    • Place of Presentation
      グランキューブ大阪(大阪)
    • Year and Date
      2009-12-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Lactobacillus gasseri OLL2809の経口投与によるDO11.10マウスの経口免疫寛容誘導の強化2009

    • Author(s)
      吉田綾子, 他
    • Organizer
      日本免疫学会 2009年度大会
    • Place of Presentation
      グランキューブ大阪(大阪)
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 分化誘導により成熟型の性質をしめるマウス小腸上皮細胞株の増殖型と成熟型の免疫機能の比較解析2009

    • Author(s)
      岩本拓, 他
    • Organizer
      日本農芸化学会関東支部2009年度大会
    • Place of Presentation
      玉川大学(東京)
    • Year and Date
      2009-10-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] 経口免疫寛容条件下でLactobacillus gasseri OLL2809生菌体投与により誘導される脾臓T細胞サブセットの解析2009

    • Author(s)
      吉田綾子, 他
    • Organizer
      日本農芸化学会関東支部2009年度大会
    • Place of Presentation
      玉川大学(東京)
    • Year and Date
      2009-10-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] 培養細胞を用いたin vitro実験から見えてくる機能2009

    • Author(s)
      清水誠、戸塚護
    • Organizer
      第13回腸内細菌学会
    • Place of Presentation
      北里大学(東京)
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス小腸、大腸由来上皮細胞株における免疫関連分子の発現および微生物成分に対する応答の比較解析2009

    • Author(s)
      岩本拓
    • Organizer
      第5回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2009-05-26
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Lactobacillus gasseri OLL2809の生菌体によるDO11.10マウスの経口免疫寛容強化機構の解析2009

    • Author(s)
      吉田綾子, 他
    • Organizer
      第5回日本食品免疫学会学術大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2009-05-26
    • Related Report
      2009 Annual Research Report
  • [Book] 食品と免疫・アレルギー事典2011

    • Author(s)
      戸塚護
    • Total Pages
      488
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report
  • [Book] 食品と免疫・アレルギー事典2011

    • Author(s)
      戸塚護(分担執筆)
    • Total Pages
      488
    • Publisher
      朝倉書店
    • Related Report
      2011 Annual Research Report
  • [Book] ミルクの事典2009

    • Author(s)
      戸塚護
    • Total Pages
      557
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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