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CD66a-mediated crosstalk between intestinal epithelia and lymphocytes

Research Project

Project/Area Number 24590936
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAGAISHI Takashi  東京医科歯科大学, 医学部附属病院, 助教 (60447464)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tetsuya  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (70265809)
WATANABE Mamoru  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
Research Collaborator YAMAZAKI Motomi  
ONIZAWA Michio  
SUZUKI Masahiro  
WATABE Taro  
HOSOYA Akinori  
JOSE Nisha  
WANG Shuan  
TOKAI Arisa  
TSUGE Naoto  
KAWAI Risa  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords炎症性腸疾患 / 粘膜免疫 / クロストーク / サイトカイン / CD66a
Outline of Final Research Achievements

Inflammatory Bowel Disease (IBD) is characterized by unrestrained lymphocyte activation that results in the production of a variety of pro-inflammatory cytokines and other mediators. Understanding the mechanisms of lymphocyte regulation is therefore of significant importance to dysregulated mucosal inflammation such as IBD. An area that is of significant interest is the cell autonomous mechanisms of T cell regulation through proteins that have natural inhibitory functions when expressed on T lymphocytes. In this regard, we have observed that CD66a has the general property of negatively regulating T cell responses initiated by antigen presentation. Defining the mechanisms of CD66a-mediated T cell regulation will lead to a significant understanding of the manner in which manipulation of this molecule may provide insights into novel therapeutic methods for the treatment of IBD.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (54 results)

All 2015 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (28 results) (of which Invited: 3 results) Book (9 results)

  • [Journal Article] RIPK3 regulates p62-LC3 complex formation via the caspase-8-dependent cleavage of p62.2014

    • Author(s)
      Y. Matsuzawa , S. Oshima, Y. Nibe, M.Kobayashi, C. Maeyashiki, Y. Nemoto, T. Nagaishi, R. Okamoto R, K. Tsuchiya, T. Nakamura, M. Watanabe.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 456(1) Issue: 1 Pages: 298-304

    • DOI

      10.1016/j.bbrc.2014.11.075

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon2014

    • Author(s)
      Fukuda M, Mizutani T, Mochizuki W, Matsumoto T, Nozaki K, Sakamaki Y, Ichinose S, Okada Y, Tanaka T, Watanabe M, Nakamura T
    • Journal Title

      Genes & Development

      Volume: 28(16) Issue: 16 Pages: 1752-1757

    • DOI

      10.1101/gad.245233.114

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparison of Magnetic Resonance and Balloon Enteroscopic Examination of Deep Small Intestine in Patients with Crohn's Disease.2014

    • Author(s)
      Takenaka K, Ohtsuka K,Watanabe M et al
    • Journal Title

      Gastroenterology

      Volume: [Epub ahead of print] Issue: 2 Pages: 334-342

    • DOI

      10.1053/j.gastro.2014.04.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myosin light chain kinase expression induced via tumor necrosis factor receptor 2 signaling in the epithelial cells regulates the development of colitis-associated carcinogenesis.2014

    • Author(s)
      Suzuki M, Nagaishi T, Yamazaki M, Onizawa M, Watabe T, Sakamaki Y, Ichinose S, Totsuka M, Oshima S, Okamoto R, Shimonaka M, Yagita H, Nakamura T, Watanabe M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 2 Pages: e88369-e88369

    • DOI

      10.1371/journal.pone.0088369

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4+ memory T cells.2013

    • Author(s)
      Nemoto Y, Nakamura T, Watanabe M et al
    • Journal Title

      Gut.

      Volume: 62 Issue: 8 Pages: 1142-1152

    • DOI

      10.1136/gutjnl-2012-302029

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Th1/Th17-Mediated Interstitial Pneumonia in Chronic Colitis Mice Independent of Intestinal Microbiota.2013

    • Author(s)
      Nemoto Y, Watanabe M et al
    • Journal Title

      J Immunol.

      Volume: 190 Issue: 12 Pages: 6616-6625

    • DOI

      10.4049/jimmunol.1202930

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury.2013

    • Author(s)
      Fordham RP, Yui S, Nakamura T, Watanabe M et. al
    • Journal Title

      Cell Stem Cell

      Volume: 13 Issue: 6 Pages: 734-744

    • DOI

      10.1016/j.stem.2013.09.015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.2013

    • Author(s)
      Watanabe M, Nishino H, Sameshima Y, Ota A, Nakamura S, Hibi T
    • Journal Title

      Aliment pharmacol ther

      Volume: 38 Issue: 3 Pages: 264-273

    • DOI

      10.1111/apt.12362

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of QD and TID oral mesalazine for maintenance of remission in quiescent ulcerative colitis: a double-blind, double-dummy, randomized multicenter study.2013

    • Author(s)
      Watanabe M, Hanai H, Nishino H, Yokoyama T, Terada T, Suzuki Y
    • Journal Title

      Inflamm Bowel Dis

      Volume: 19 Issue: 8 Pages: 1681-90

    • DOI

      10.1097/mib.0b013e318286fa3d

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice.2013

    • Author(s)
      Takahara M, Nemoto Y, Oshima S, Matsuzawa Y, Kanai T, Okamoto R, Tsuchiya K, Nakamura T, Yamamoto K, Watanabe M.
    • Journal Title

      Immunol Lett.

      Volume: 156 Issue: 1-2 Pages: 82-93

    • DOI

      10.1016/j.imlet.2013.09.001

    • NAID

      120005468269

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lineage-specific expression of Bestrophin-2 and Bestrophin-4 in human intestinal epithelial cells.2013

    • Author(s)
      Ito G, Okamoto R, Nakamura T, Watanabe M et al
    • Journal Title

      PloS One.

      Volume: 8 Issue: 11 Pages: e79693-e79693

    • DOI

      10.1371/journal.pone.0079693

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction2012

    • Author(s)
      Chen L, Chen Z, Baker K, Halvorsen EM, da Cunha AP, Flak MB, Gerber G, Huang YH, Hosomi S, Arthur JC, Dery KJ, Nagaishi T, Beauchemin N, Holmes KV, Ho JW, Shively JE, Jobin C, Onderdonk AB, Bry L, Weiner HL, Higgins DE, Blumberg RS
    • Journal Title

      Immunity

      Volume: 37 Issue: 5 Pages: 930-946

    • DOI

      10.1016/j.immuni.2012.07.016

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+stem cell2012

    • Author(s)
      Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, and Watanabe M
    • Journal Title

      Nature Medicine

      Volume: 18 Issue: 4 Pages: 618-623

    • DOI

      10.1038/nm.2695

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Real-time analysis of P-glycoprotein-mediated drug transport across primary intestinal epithelium three-dimensionally cultured in vitro2012

    • Author(s)
      Mizutani T, Nakamura T, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 419 Issue: 2 Pages: 238-243

    • DOI

      10.1016/j.bbrc.2012.01.155

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The development of colitogenic CD4+ T cells is regulated by IL-7 in collaboration with natural killer cell function in a murine model of colitis2012

    • Author(s)
      Yamaji O, Totsuka T
    • Journal Title

      J Immunol

      Volume: 188 Issue: 6 Pages: 2524-2536

    • DOI

      10.4049/jimmunol.1100371

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] NK細胞はIL-7と協調し腸炎惹起性T細胞の分化増殖を抑制する.2012

    • Author(s)
      永石宇司, 渡辺守、 他.
    • Journal Title

      日本臨床免疫学会誌

      Volume: 36

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 慢性大腸炎モデルにおける腸炎惹起性T細胞の増殖はIL-7とNK細胞により制御される2012

    • Author(s)
      永石宇司、渡辺 守、他
    • Journal Title

      消化器と免疫

      Volume: in press

    • Related Report
      2012 Research-status Report
  • [Presentation] シンポジウム「内胚葉系臓器の再生医療と幹細胞生物学」培養細胞移植実験を利用する腸管上皮幹細胞解析2015

    • Author(s)
      中村哲也
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 大腸上皮細胞特異的なTNFシグナルによるIBD合併大腸癌発生機構の解析2015

    • Author(s)
      永石宇司、渡部太郎、鈴木雅博、Jose Nisha、東海有沙、細谷明徳、鬼沢道夫、中村哲也、渡辺守
    • Organizer
      第11回日本消化管学会総会学術集会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2015-02-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] TNFR2 signaling in the epithelia may be involved in the development of colitis-associated tumor.2014

    • Author(s)
      Watabe T, Nagaishi T, Suzuki M, Yamazaki M, Onizawa M, Jose N, Tokai A, Hosoya A, Totsuka M, Yagita H, Watanabe M
    • Organizer
      第43回日本免疫学会総会学術集会
    • Place of Presentation
      Kyoto International Conference Center (Kyoto)
    • Year and Date
      2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] タクロリムスを使用した難治性潰瘍性大腸炎の内視鏡的検討2014

    • Author(s)
      齊藤詠子、大塚和朗、竹中健人、藤井俊光、永石宇司、長堀正和、渡辺守
    • Organizer
      第99回日本消化器内視鏡学会関東地方会
    • Place of Presentation
      シェーンバッハ砂防(東京)
    • Year and Date
      2014-12-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] The expression of myosin light chain kinase induced by NF-kB activation is involved in the development of colitis-associated cancer.2014

    • Author(s)
      Jose N, Nagaishi T, Watabe T, Tokai A, Suzuki M, Yamazaki M, Watanabe M
    • Organizer
      United European Gastroenterology Week 2014
    • Place of Presentation
      Vienna (Austria)
    • Year and Date
      2014-10-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Epithelial MLCK induced via NF-kB activation may be involved in the development of colitis-associated carcinogenesis.2014

    • Author(s)
      Watabe T, Nagaishi T, Suzuki M, Yamazaki M, Jose N, Tokai A, Watanabe M
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      Pacifico Yokohama (神奈川)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 培養腸管上皮幹細胞移植と組織再生2014

    • Author(s)
      中村哲也
    • Organizer
      第73回 日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸管上皮における特異的TNFシグナルはIBD合併大腸癌の発生を促進させる2014

    • Author(s)
      渡部太郎、永石宇司、鈴木雅博、山崎元美、鬼沢道夫、Jose Nisha、東海有沙、渡辺守
    • Organizer
      免疫サマースクール 2014
    • Place of Presentation
      オリビアン小豆島(香川)
    • Year and Date
      2014-07-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸管上皮細胞における特異的TNFシグナルはIBD合併大腸癌の発生を促進させる2014

    • Author(s)
      渡部太郎、永石宇司、鈴木雅博、山崎元美、鬼沢道夫、Jose Nisha、東海有沙、渡辺守
    • Organizer
      第51回日本消化器免疫学会総会
    • Place of Presentation
      京都大学芝蘭会館(京都)
    • Year and Date
      2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Myosin light chain kinase induced by NF-kB is involved in the development of colitis-associated carcinogenesis.2014

    • Author(s)
      Nagaishi T, Suzuki M, Yamazaki M, Onizawa M, Watabe T, Watanabe M
    • Organizer
      Federation of Clinical Immunology Societies 2014
    • Place of Presentation
      Chicago (U.S.A.)
    • Year and Date
      2014-06-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] IBD合併大腸癌モデルの発生過程における上皮細胞特異的TNFシグナルの解析2014

    • Author(s)
      鈴木雅博、永石宇司、鬼澤道夫、山崎元美、渡辺守
    • Organizer
      第100回日本消化器病学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 消化管幹細胞研究の新たな展開 培養腸管上皮細胞移植における幹細胞の挙動2014

    • Author(s)
      中村哲也、渡辺 守
    • Organizer
      第100回 日本消化器病学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Natural killer cells abrogate an animal model of colitis by targeting the early stage of pathogenic T cell development.2013

    • Author(s)
      Nagaishi T, Yamaji O, Onizawa M, Suzuki M, Kanai T, Watanabe M
    • Organizer
      AGA 2013
    • Place of Presentation
      Orlando(USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Myosin Light Chain Kinase is Involved in the Development of an Animal Model of Colitis-Associted Tumor.2013

    • Author(s)
      Suzuki M, Nagaishi T, Onizawa M, Yamazaki M, Tsuge N, Watanabe M
    • Organizer
      11th International Congress of Mucosal Immunology
    • Place of Presentation
      Vancouver(Canada)
    • Related Report
      2013 Research-status Report
  • [Presentation] Natural killer cells regulate the early stage of pathogenic T cell development in an IBD models.2013

    • Author(s)
      Nagaishi T, Yamaji O, Suzuki M, Yamazaki M, Watanabe M
    • Organizer
      UEGW 2013
    • Place of Presentation
      Berlin(Germany)
    • Related Report
      2013 Research-status Report
  • [Presentation] 炎症性腸疾患の病態理解と実験モデル2013

    • Author(s)
      永石 宇司、渡辺 守
    • Organizer
      日本臨床免疫学会 2013
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Myosin light chain kinase induced by NF-kB is involved in the development of colitis-associated cancer.2013

    • Author(s)
      Suzuki M, Nagaishi T, Onizawa M, Yamazaki M, Yagita H, Watanabe M
    • Organizer
      日本免疫学会 2013
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Related Report
      2013 Research-status Report
  • [Presentation] クローン病感受性遺伝子A20による腸炎惹起機構

    • Author(s)
      大島 茂、松沢 優、高原政宏、小林正典、仁部洋一、前屋舗千明、永石宇司、土屋輝一郎、岡本隆一、中村哲也、渡辺 守
    • Organizer
      厚生労働科学研究 難治性疾患克服研究事業 「難治性炎症性腸管障害に関する調査研究」
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Natural killer cells regulate the early stage of pathogenic T cell development in a murine model of colitis.

    • Author(s)
      Nagaishi T, Watanabe M et al.
    • Organizer
      Immuno 2013
    • Place of Presentation
      Barcelona
    • Related Report
      2012 Research-status Report
  • [Presentation] Natural killer cells regulate the early stage of pathogenic T cell development in a murine model of colitis.

    • Author(s)
      Nagaishi T.
    • Organizer
      IDIBAPS-Center Esther Koplowitz
    • Place of Presentation
      Barcelona
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Natural killer cells suppress an animal model of colitis by targeting the early stage of pathogenic T cell development.

    • Author(s)
      Nagaishi T, Watanabe M et al.
    • Organizer
      日本免疫学会総会 2012
    • Place of Presentation
      Kobe
    • Related Report
      2012 Research-status Report
  • [Presentation] Natural killer cells suppress an animal model of IBD by targeting the early stage of pathogenic T cell development.

    • Author(s)
      Nagaishi T, Watanabe M et al.
    • Organizer
      Asian IBD Symposium 2012
    • Place of Presentation
      Seoul
    • Related Report
      2012 Research-status Report
  • [Presentation] Natural killer cells suppress an animal model of IBD by targeting the early stage of pathogenic T cell development.

    • Author(s)
      永石宇司, 渡辺守、 他.
    • Organizer
      日本臨床免疫学会総会 2012
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 慢性大腸炎モデルにおける腸炎惹起性T細胞の増殖はIL-7とNK細胞により制御される.

    • Author(s)
      永石宇司, 渡辺守、 他.
    • Organizer
      日本消化器免疫学会総会 2012
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] Natural killer cells regulate colitis by targeting the early stage of pathogenic T cell development.

    • Author(s)
      Nagaishi T, Watanabe M et al.
    • Organizer
      Federation of Clinical Immunology Societies 2012
    • Place of Presentation
      Vancouver
    • Related Report
      2012 Research-status Report
  • [Presentation] Regeneration of damaged colon epithelium by transplanted colon Lgr5+ stem cells maintained and expanded in vitro.

    • Author(s)
      Yui S, Nakamura T, Nagaishi T, Watanabe M et al.
    • Organizer
      幹細胞シンポジウム
    • Place of Presentation
      Awajishima
    • Related Report
      2012 Research-status Report
  • [Presentation] 単一幹細胞からの大腸上皮大量培養と細胞移植による大腸上皮再生.

    • Author(s)
      中村哲也、渡辺 守
    • Organizer
      日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 培養大腸上皮細胞による消化管再生へのアプローチ.

    • Author(s)
      中村哲也、渡辺 守
    • Organizer
      日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Book] 分子消化器病2014

    • Author(s)
      渡辺 守
    • Total Pages
      1
    • Publisher
      先端医学社
    • Related Report
      2014 Annual Research Report
  • [Book] GI Research2014

    • Author(s)
      渡辺 守
    • Total Pages
      2
    • Publisher
      先端医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 実験医学2014

    • Author(s)
      渡辺 守、他
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report
  • [Book] GI Research2014

    • Author(s)
      中村哲也、他
    • Total Pages
      7
    • Publisher
      先端医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 最新医学 68巻6号2013

    • Author(s)
      永石宇司、藤井俊光、渡辺 守
    • Publisher
      最新医学社
    • Related Report
      2013 Research-status Report
  • [Book] 最新医学 68巻6月号2013

    • Author(s)
      永石 宇司、藤井 俊光、渡辺 守
    • Publisher
      最新医学社
    • Related Report
      2013 Research-status Report
  • [Book] GI Research2012

    • Author(s)
      鈴木雅博、永石宇司、渡辺 守
    • Publisher
      先端医学社
    • Related Report
      2012 Research-status Report
  • [Book] 分子消化器病2012

    • Author(s)
      中村哲也、渡辺 守、他
    • Publisher
      先端医学社
    • Related Report
      2012 Research-status Report
  • [Book] 内科学2012

    • Author(s)
      中村哲也
    • Publisher
      西村書店
    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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