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CEACAM1 regulates the cytokine network in intestinal mucosa

Research Project

Project/Area Number 20590737
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAGAISHI Takashi  Tokyo Medical and Dental University, 医学部附属病院, 助教 (60447464)

Co-Investigator(Renkei-kenkyūsha) NAKAMURA Tetsuya  東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (70265809)
TSUCHIYA Kiichiro  東京医科歯科大学, 医学部附属病院, 講師 (40376786)
WATANABE Mamoru  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsCEACAM1 / リンパ球 / 粘膜免疫 / サイトカイン / シグナル伝達
Research Abstract

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 carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has the general property of negatively regulating T cell responses that are initiated by antigen/MHC complex-mediated signals. Moreover, we have demonstrated that this is clinically relevant, as CEACAM1 functions in the suppression of an IBD model. Defining the mechanisms of CEACAM1-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)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (59 results)

All 2011 2010 2009 2008

All Journal Article (21 results) (of which Peer Reviewed: 13 results) Presentation (34 results) Book (4 results)

  • [Journal Article] 腹部症状発現メカニズム解明への臨床的アプローチ:腸内細菌、炎症と腹部症状2011

    • Author(s)
      永石宇司、山地統、渡辺守
    • Journal Title

      Modern Physician 31

      Pages: 311-313

    • Related Report
      2010 Final Research Report
  • [Journal Article] 腹部癌状発現メカニズム解明への臨床的アプローチ:腸内細菌、炎症と腹部症状2011

    • Author(s)
      永石宇司、山地統、渡辺守
    • Journal Title

      Modern Physician

      Volume: 31 Pages: 311-313

    • Related Report
      2010 Annual Research Report
  • [Journal Article] CEACAM1 によるシグナル伝達2009

    • Author(s)
      永石宇司
    • Journal Title

      分子消化器病 6

      Pages: 173-177

    • Related Report
      2010 Final Research Report
  • [Journal Article] ヒスチジン栄養療法はマクロファージの炎症性サイトカイン産生を抑制して腸炎モデルを改善させる2009

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

      Review of Gastroenterology & ClinicalGastroenterology and Hepatology 4(2)

      Pages: 42-45

    • Related Report
      2010 Final Research Report
  • [Journal Article] Highmobility group box 1 contributes tolethality of endotoxemia in hemeoxygenase-1 deficient mice.2009

    • Author(s)
      Takamiya R, Nagaishi T, et al.
    • Journal Title

      Am JRespir Cell Mol Biol 41

      Pages: 129-135

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] N-glycanmoieties in FcRn determine steady-statemembrane distribution and directionaltransport of IgG.2009

    • Author(s)
      Kuo T, Nagaishi T, et al.
    • Journal Title

      J Biol Chem 284

      Pages: 8292-8300

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathway via TNF /NF B inintestinal epithelial cells may bedirectly involved in colitis-associatedcarcinogenesis.2009

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Journal Title

      Am J Physiol Gastro-intest Liver Physiol 296

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1 deficient mice.2009

    • Author(s)
      Takamiya R, Nagaishi T, et al.
    • Journal Title

      Am J Respir Cell Mol Biol. 41

      Pages: 129-135

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-glycan moieties in FcRn determine steady-state membrane distribution and directional transport of IgG.2009

    • Author(s)
      Kuo T, Nagaishi T, et al.
    • Journal Title

      J Biol Chem. 284

      Pages: 8292-8300

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathway via TNFα/NFκB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenes is.2009

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol. 296

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

    • Author(s)
      永石宇司
    • Journal Title

      分子消化器病(CEACAM1によるシグナル伝達)

      Pages: 63-67

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

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

      Review of Gastroenterology & Clinical Gastroenterology and Hepatology(ヒスチジン栄養療法はマクロファージの炎症性サイトカイン産生を抑制して腸炎モデルを改善させる)

      Pages: 42-45

    • Related Report
      2009 Annual Research Report
  • [Journal Article] High mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1 deficient mice.2009

    • Author(s)
      Takamiya R, Nagaishi T, etal.
    • Journal Title

      Am J Respir Cell Mol Biol. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-glycan moieties in FcRn determine steady-state membrane distribution and directional transport of IgG.2009

    • Author(s)
      Kuo T, Nagaishi T, et al
    • Journal Title

      J Biol Chem. (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathway via TNFa/NFKB in intestinal epithelial cellS may be directly involved in colitis-associated carcinogenesis.2009

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol. (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腸管免疫における免疫寛容機構破綻の病態解明および新規治療法の開発2008

    • Author(s)
      永石宇司
    • Journal Title

      アレルギア 37

      Pages: 57-60

    • Related Report
      2010 Final Research Report
  • [Journal Article] Microsomal triglyceride transfer proteinによるNKT細胞介在性肝炎および腸炎の制御2008

    • Author(s)
      永石宇司, ほか
    • Journal Title

      消化器と免疫 44

      Pages: 7-10

    • Related Report
      2010 Final Research Report
  • [Journal Article] CEACAM1 andthe regulation of mucosal inflammation.2008

    • Author(s)
      永石宇司, et al.
    • Journal Title

      Mucosal Immunology 1

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carcinoembryonic antigen-related cell adhesionmolecule 1 inhibits proximal TCR signaling by targeting ZAP-70.2008

    • Author(s)
      Chen Z, Nagaishi T, et al.
    • Journal Title

      J Immunol 180

      Pages: 6085-6093

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70.2008

    • Author(s)
      Chen z, Nagaishi T, et al.
    • Journal Title

      J Immunol. 180

      Pages: 6085-6093

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CEACAMl and the regulation of mucosal inflammation.2008

    • Author(s)
      Naeaishi T, et al.
    • Journal Title

      Mucosal Immunology 1

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] TNF- /NFBpathways in intestinal epithelialcells maybe directly involved in colitis-associatedcarcinogenesis.2010

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      The 4th Japanand USCollaboration Conference in Gastroenterology.
    • Place of Presentation
      東京
    • Year and Date
      2010-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] TNF・α/NF・kB pathways in intestinal epithelial cells may be dhrectly involved in colitis-associated carcinogenesis.2010

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Organizer
      The 4^<th> Japan and US Collaboration Conference in Gastroenterology
    • Place of Presentation
      東京
    • Year and Date
      2010-11-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] A well-definedculture system for colonic epithelial cells thatallows efficient enrichment of LGR5+ stemcells.2010

    • Author(s)
      Yui S, Nagaishi T, et al.
    • Organizer
      The 1stJSGE International TopicConference -Stem Cells in Digestive Organs.
    • Place of Presentation
      鎌倉
    • Year and Date
      2010-09-26
    • Related Report
      2010 Final Research Report
  • [Presentation] A well defined culture system for colonic epithelial cells that allows efficient enrichment of LGR5+stem cells.2010

    • Author(s)
      Yui S, Nagaishi T, et al.
    • Organizer
      The 1^<st> JSGE International Topic Conference-Stem Cells in Digestive Organs
    • Place of Presentation
      鎌倉
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] TNF pathwayin intestinal epithelial cells may bedirectly involved in colitis-associated carcinogenesis.2010

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      国際免疫学会議
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-25
    • Related Report
      2010 Final Research Report
  • [Presentation] TNF pathway in intestinal epithelial cells may be directly involved in colitis associated carcinogenesis.2010

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Organizer
      国際免疫学会議
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Myosinlight chain kinase is associated withdisruption of epithelial tight junction in ananimal model of colitis-associated tumor.2010

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      アメリカ臨床免疫学会
    • Place of Presentation
      ボストン
    • Year and Date
      2010-06-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Myosin light chain kinase is associated with disruption of epithelialtight junction in an animal model of colitis associated tumor.2010

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Organizer
      アメリカ臨床免疫学会
    • Place of Presentation
      ボストン
    • Year and Date
      2010-06-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Myosinlight chain kinase is associated with dis-ruption of epithelial tight junction in colitis-associated tumor.2010

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      ニューオリンズ
    • Year and Date
      2010-05-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Myosin light chain kinase is associated with disruption of epithelialtight junction in colitis associated tumor.2010

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      ニューオリンズ
    • Year and Date
      2010-05-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Report of CCFA annual meeting, 2009 Advances in Inflammatory Bowel Diseases ---Basic Science---2010

    • Author(s)
      永石宇司
    • Organizer
      The 4^<th> Korea-Japan Inflammatory Bowel Disease Symposium
    • Place of Presentation
      東京
    • Year and Date
      2010-01-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Tumor necrosisfactor receptor signaling in intestinal epitheliamay be directly involved in colitis-associatedcarcinogenesis.2009

    • Author(s)
      永石宇司, et al.
    • Organizer
      Advances in InflammatoryBowel Diseases.
    • Place of Presentation
      マイアミ
    • Year and Date
      2009-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumor necrosis factor receptor signaling in intestinal epithelia maybe directly involved in colitis-associated carcinogenesis2009

    • Author(s)
      永石宇司, et al.
    • Organizer
      Advances in Inflammatory Bowel Diseases
    • Place of Presentation
      マイアミ
    • Year and Date
      2009-12-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] TNFreceptor signaling in intestinal epithelia maybe directly involved in colitis-associatedcarcinogenesis.2009

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      国際粘膜免疫学会議
    • Place of Presentation
      ボストン
    • Year and Date
      2009-07-07
    • Related Report
      2010 Final Research Report
  • [Presentation] TNF receptor signaling in intestinal epithelia may be directly involved in colitis-associated carcinogenesis2009

    • Author(s)
      Onizawa M, 永石宇司, et al.
    • Organizer
      国際粘膜免疫学会議
    • Place of Presentation
      ボストン
    • Year and Date
      2009-07-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Tumor necrosis factor receptor signaling inintestinal epithelial cells may be directlyinvolved in colitis-associated carcinogenesis.2009

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      アメリカ臨床免疫学会
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2009-06-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumor necrosis factor receptor signaling in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis2009

    • Author(s)
      Onizawa M, 永石宇司, et al.
    • Organizer
      アメリカ臨床免疫学会
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2009-06-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Tumor necrosis factor receptor signaling inintestinal epithelial cells may be directlyinvolved in colitis-associated carcinogenesis.2009

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      シカゴ
    • Year and Date
      2009-06-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumor necrosis factor receptor signaling in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis2009

    • Author(s)
      Onizawa M, 永石宇司, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      シカゴ
    • Year and Date
      2009-06-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] CEACAM1 regulatesT cell function in IBD.2009

    • Author(s)
      永石宇司
    • Organizer
      Surface BarrierImmunology Study Group Meeting.
    • Place of Presentation
      東京
    • Year and Date
      2009-03-07
    • Related Report
      2010 Final Research Report
  • [Presentation] CEACAMl regulates T cell function in IBD2009

    • Author(s)
      Nagaishi T
    • Organizer
      Surface Barrier Immunology Study GroupMeeting
    • Place of Presentation
      東京
    • Year and Date
      2009-03-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Neutralization of tumor necrosis factorsuppresses the development of colitis associated tumor in mice.2009

    • Author(s)
      鬼沢道夫, 永石宇司, ほか
    • Organizer
      日本炎症性腸疾患学会
    • Place of Presentation
      東京
    • Year and Date
      2009-02-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Neutralization of tumor necrosis factor suppresses the development of colitis associated tumor in mice2009

    • Author(s)
      鬼沢道夫, 永石宇司, ほか
    • Organizer
      日本炎症性腸疾患学会
    • Place of Presentation
      東京
    • Year and Date
      2009-02-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] CEACAM1による腸管粘膜免疫の調節機構2008

    • Author(s)
      永石宇司, ほか
    • Organizer
      浜名湖シンポジウム
    • Place of Presentation
      浜松
    • Year and Date
      2008-12-20
    • Related Report
      2010 Final Research Report
  • [Presentation] CEACAMlによる腸管粘膜免疫の調節機構2008

    • Author(s)
      永石宇司, ほか
    • Organizer
      浜名湖シンポジウム
    • Place of Presentation
      浜松
    • Year and Date
      2008-12-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 動物モデルによる抗TNF抗体療法による炎症性腸疾患合併大腸癌の抑制の検討2008

    • Author(s)
      鬼沢道夫, 永石宇司, ほか
    • Organizer
      日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] CEACAM1 regulates Tcell function in an IBD model.2008

    • Author(s)
      永石宇司
    • Organizer
      21stCentury Forum.
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] N-glycanmoieties in FcRn determines steady-state membrane distribution anddirectional trafficking but not cross-species IgG binding.2008

    • Author(s)
      Kuo T, Nagaishi T, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Neutralization of tumor necrosis factorsuppresses the development of colitisassociated tumor in mice.2008

    • Author(s)
      鬼沢道夫, 永石宇司, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Neutralization of tumor necrosis factor suppresses the development of colitis associated tumor in mice2008

    • Author(s)
      Onizawa M, Nagaishi T, et al.
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] N-glycan moieties in FcRn determines steady-state membranedistribution and directional trafficking but not cross-species lgG binding.2008

    • Author(s)
      Kuo T, Nagaishi T, etal
    • Organizer
      アメリカ消化器病学会
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] CEACAMl regulates T cell function in an IBD model2008

    • Author(s)
      Nagaishi T
    • Organizer
      21st Century Forum
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Updated for anti-TNFbehavior for Crohn's disease.2008

    • Author(s)
      永石宇司
    • Organizer
      MCBClub Meeting.
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-20
    • Related Report
      2010 Final Research Report
  • [Presentation] Updated for anti-TNFα behavior for Crohn's disease.2008

    • Author(s)
      Naeaishi T
    • Organizer
      MCB Club Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-20
    • Related Report
      2008 Annual Research Report
  • [Book] 炎症性腸疾患:腸管粘膜免疫の特殊性2010

    • Author(s)
      永石宇司、渡辺守
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Book] 臨床粘膜免疫学:潰瘍性大腸炎2010

    • Author(s)
      永石宇司、渡辺守
    • Publisher
      シナジー
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Book] 消化器と免疫2008

    • Author(s)
      永石宇司, ほか
    • Publisher
      Microsomal triglyceride transfer proteinによるNKT細胞介在性肝炎および腸炎の制御
    • Related Report
      2008 Annual Research Report
  • [Book] アレルギア2008

    • Author(s)
      永石宇司
    • Publisher
      腸管免疫における免疫寛容機構破綻の病態解明および新規治療法の開発
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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