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Study of the pathogenesis of autoimmune pancreatitis and, the relation to activation of immate immunity induced by bacteria

Research Project

Project/Area Number 23590522
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo Women's Medical University

Principal Investigator

HARUTA Ikuko  東京女子医科大学, 医学部, 准教授 (80221513)

Co-Investigator(Kenkyū-buntansha) YAGI Junji  東京女子医科大学, 医学部, 教授 (70182300)
Project Period (FY) 2011-04-28 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自己免疫性膵炎 / IgG4関連疾患 / 自然免疫 / FliC / 自己免疫疾患 / 制御性T細胞 / 自己免疫性膵炎(AIP) / 細菌 / IgG4関連疾患(IgG4-RD) / 自己抗原 / IgG4関連腎疾患(IgG4-RKD) / 自己抗体 / 自己免疫性膵炎(AIP) / メモリーT細胞 / IgG4-RD(IgG4関連疾患) / 分子擬態 / 慢性炎症 / 分子相同性
Outline of Final Research Achievements

We previously established a mouse model of AIP using chronic exposure to a commensal bacteria, Escherichia coli, leading to pancreatic inflammation, and elevation in IgG and IgG1 in serum and detection of anti-lactoferrin and anticarbonic anhydrace-II. The outer membrane fractions of E. coli were subjected to two-dimensional gel electrophoresis followed by immunoblotting against sera from the AIP model. One representative immunoreactive spot was determined using TOF/MS and Mascot search as FliC. Sera from patients with AIP had a signiticcantly higher antibody titer. Therefore, we are underway to clarify the possibility of a new diagnostic value of anti FliC-Ab titer.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (32 results)

All 2015 2014 2013 2012 2011

All Journal Article (10 results) (of which Acknowledgement Compliant: 1 results,  Peer Reviewed: 7 results) Presentation (22 results)

  • [Journal Article] 自己免疫性膵炎の動物モデル2015

    • Author(s)
      春田郁子, 清水京子, 柳沢直子, 古川徹, 立元敬子, 八木淳二
    • Journal Title

      肝胆膵

      Volume: 70(2) Pages: 201-209

    • Related Report
      2014 Research-status Report
    • Acknowledgement Compliant
  • [Journal Article] 表題 Identification of commensal flora-associated antigen as a pathogenetic factor of autoimmune pancreatitis2014

    • Author(s)
      YANAGISAWA Naoko, HARUTA Ikuko, SHIMIZU Kyoko, FURUKAWA Toru, HIGUCHI Tomoaki, SHIBATA Noriyuki, SHIRATORI Keiko, YAGI Junji
    • Journal Title

      Pancreatology

      Volume: 14 Pages: 100-106

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 自己免疫性膵炎と共生細菌2014

    • Author(s)
      春田郁子, 清水京子, 古川徹, 柳沢直子, 八木淳二, 白鳥敬子
    • Journal Title

      膵臓

      Volume: 29 Pages: 59-66

    • NAID

      130004496052

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mouse monoclonal antibody specific for outer membrane protein A of <I>Escherichia coli</I>2013

    • Author(s)
      ABE Yoshihiro, HARUTA Ikuko, YANAGISAWA Naoko, YAGI Junji
    • Journal Title

      Monoclonal antibodies in immunodiagnosis and immunotherapy

      Volume: 32(1) Issue: 1 Pages: 32-35

    • DOI

      10.1089/mab.2012.0069

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Commensal flore, is it an unwelcomed companion as a triggering factor of autoimmune pancreatitis?2012

    • Author(s)
      HARURA Ikuko, SHIMIZU Kyoko, YANAGISAWA Naoko, SHIRATORI Keiko, YAGI Junji
    • Journal Title

      Frontiers in Physiology

      Volume: 3(Article 77) Pages: 1-8

    • DOI

      10.3389/fphys.2012.00077

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of commensal bacteria may lead to dysregulated inflammatory and autoimmune responses in a mouse model for chronic nonsuppurative destructive cholangitis2012

    • Author(s)
      HARUTA Ikuko, KIKUCHI Ken, NAKAMURA Minoru, HIROTA Katsuhiko, KATO Hidehito, MIYAKAWA Hiroshi, SHIBATA Noriyuki, MIYAKE Yoichiro, HASHIMOTO Etsuko, SHIRATORI Keiko, YAGI Junji
    • Journal Title

      Journal of clinical immunology

      Volume: 32(5) Issue: 5 Pages: 1026-1037

    • DOI

      10.1007/s10875-012-9712-1

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細菌感染と自己免疫性膵炎2012

    • Author(s)
      春田郁子、柳沢直子、八木淳二
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 57 Pages: 139-144

    • Related Report
      2011 Research-status Report
  • [Journal Article] Are dysregulated inflammatory responses to commensal bacteria involved in the pathogenesis of hepato-biliary-pancreatic autoimmune disease? an analysis using mice models of primary biliary cirrhosis and autoimmune pancreatitis2011

    • Author(s)
      Yanagisawa N, Haruta I, Kikuchi K, Shibata N, Yagi J
    • Journal Title

      ISRN Gastroenterol

      Volume: 2011(2011)(e-publ;ished) Pages: 8-8

    • DOI

      10.5402/2011/513514

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distant skin inflammation induced by chronic bacterial exposure to abdominal subcutaneous tissue in nonalcoholic fatty liver disease-harboring mice2011

    • Author(s)
      Hidehiro Ueshiba, Ikuko Haruta, Noriko Matsushita, Naoko Ishiguro, Etsuko Hashimoto, Junji Yagi
    • Journal Title

      Journal of Tokyo Women's Medical University

      Volume: 81 Pages: 102-110

    • NAID

      110008462587

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細菌と自己免疫性疾患(原発性胆汁性肝硬変)2011

    • Author(s)
      春田郁子、柳沢直子、八木淳二
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 55 Pages: 390-396

    • Related Report
      2011 Research-status Report
  • [Presentation] The role of bacterial component in the progression of non-alcohol fatty liver disease2015

    • Author(s)
      春田 郁子, 大坂 利文, 松下 典子, 柳沢 直子, 上芝 秀博, 常田 聡, 八木 淳二
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      長良川国際会議場(岐阜県・岐阜市)
    • Year and Date
      2015-03-23 – 2015-03-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 自己免疫性膵炎に関するアジュバント効果の検討2015

    • Author(s)
      阿部義廣, 春田郁子, 柳沢直子, 大森深雪, 樋口智昭, 上芝秀博, 八木淳二
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      長良川国際会議場(岐阜県・岐阜市)
    • Year and Date
      2015-03-23 – 2015-03-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Possible involvement of FliC from Escherichia coli as a pathogenic factor of IgG4-related disease2014

    • Author(s)
      Tomoaki Higuchi, Yoshihiro Abe, Ikuko Haruta, Naoko Yanagisawa, Miyuki Omori-Miyake, Hidehiro Ueshiba, Junji Yagi
    • Organizer
      第43回日本免疫学会総会
    • Place of Presentation
      国立京都国際会館(京都府、京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Could microorganisms-originated adjuvant be a triggering factor of IgG4-related disease?2014

    • Author(s)
      Yoshihiro Abe, Tomoaki Higuchi, Ikuko Haruta, Naoko Yanagisawa, Miyuki Omori-Miyake, Hidehiro Ueshiba, Junji Yagi
    • Organizer
      第43回日本免疫学会総会
    • Place of Presentation
      国立京都国際会館(京都府、京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] マウスモデルを用いたNAFLD/NASH病態と腸内細菌叢の関連の検討2014

    • Author(s)
      春田郁子, 徳重克年, 橋本悦子
    • Organizer
      第40回日本肝臓学会東部会
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2014-11-27 – 2014-11-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Commensal flora as a pathogenic factor of autoimmune pancreatitis and associated diseases2014

    • Author(s)
      HARUTA Ikuko, YANAGISAWA Naoko, SHIMIZU Kyoko, OMORI-MIYAKE Miyuki, ABE Yoshihiro, HIGUCHI Tomoaki, FURUKAWA Toru, SHIRATORI Keiko, YAGI Junji
    • Organizer
      5th Asian-Pacific Topic Conference
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2014-10-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Extra-pancreatic involvement in repeated Escherichia coli inoculated mice harboring AIP-like pancreatitis2014

    • Author(s)
      HIGUCHI Tomoaki, HARUTA Ikuko, YANAGISAWA Naoko, SHIMIZU Kyoko, ABE Yoshihiro, OMORI-MIYAKE Miyuki, FURUKAWA Toru, SHIRATORI Keiko, YAGI Junji
    • Organizer
      5th Asian-Pacific Topic Conference
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2014-10-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 腸内細菌反復投与により誘導される自己免疫性膵炎戻るマウスにおける膵外病変の検討2014

    • Author(s)
      春田郁子, 清水京子, 古川徹, 白鳥敬子
    • 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(東京都、千代田区)
    • Year and Date
      2014-04-23 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of a commensal baceria triggered autoimmune pancreatitis mouse model2014

    • Author(s)
      HARUTA Ikuko, SHIMIZU Kyoko, YANAGISAWA Naoko, OMORI-MIYAKE Miyuki, FURUKAWA Toru, SHIBATA Noriyuki, YAGI Junji, SHIRATORI Keiko
    • Organizer
      International symposium on igG4-RD & associated conditions
    • Place of Presentation
      Honolulu, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 腸内細菌により誘導される自己免疫性膵炎モデルの膵外病変の検討2014

    • Author(s)
      樋口智昭, 春田郁子, 柳沢直子, 上芝秀博, 大森深雪, 阿部義廣, 八木淳二
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of commensal flora associated antigen, as a pathogenic factor of autoimmune pancreatitis2013

    • Author(s)
      ABE Yoshihiro, YANAGISAWA Naoko, HARUTA Ikuko, SHIRATORI Keiko, YAGI Junji
    • Organizer
      15th International congress of immunology
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Research-status Report
  • [Presentation] Analysis of the cellular phenotype in a mouse model of commensal bacteria triggerd autoimmune pancreatitis2013

    • Author(s)
      HARUTA Ikuko, OMORI-MIYAKE Miyuki, HIGUCHI Tomoaki, YANAGISAWA Naoko, ABE Yoshihiro, SHIRATORI Keiko, YAGI Junji
    • Organizer
      Annual meeting of the japanese society for immunology, 2013
    • Place of Presentation
      Chiba, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] マウスモデルを用いた自己免疫性膵炎の病原因子・疾患特異的抗体の可能性の検討2013

    • Author(s)
      春田郁子, 清水京子, 古川徹, 白鳥敬子
    • Organizer
      第44回日本膵臓学会大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 自己免疫性膵炎の病原因子としての共生細菌の関与の検討2013

    • Author(s)
      柳沢直子, 春田郁子, 阿部義廣, 八木淳二
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張
    • Related Report
      2012 Research-status Report
  • [Presentation] Commensal flora as possible pathogens of autoimmune pancreatitis2012

    • Author(s)
      HARUTA Ikuko, YANAGISAWA Naoko, SHIMIZU Kyoko, ABE Yoshihiro, OMORI-MIYAKE Miyuki, YAGI Junji, SHIRATORI Keiko
    • Organizer
      American Pancreatic Association/International Association of Pancreatology 2012 Joint Meeting
    • Place of Presentation
      Florida, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Commensal bacteria may be involved in the pathogenesis of autoimmune pancreatitis2012

    • Author(s)
      HARUTA Ikuko, OMORI-MIYAKE Miyuki, YANAGISAWA Naoko, ABE Yoshihiro, SHIRATORI Keiko, YAGI Junji
    • Organizer
      2012 Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] 自己免疫性膵炎の病原因子の可能性としての共生細菌の関与の検討2012

    • Author(s)
      春田郁子, 柳沢直子, ミヤケ深雪, 阿部義廣, 清水京子, 古川徹, 八木淳二, 白鳥敬子
    • Organizer
      第20回浜名湖シンポジウム
    • Place of Presentation
      浜松
    • Related Report
      2012 Research-status Report
  • [Presentation] 細菌が誘導する自然免疫賦活の自己免疫性膵炎及び原発性胆汁性肝硬変の発症機構への関与の検討2011

    • Author(s)
      春田郁子、清水京子、橋本悦子、白鳥敬子
    • Organizer
      第97回 日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 細菌が誘導する自然免疫賦活は自己免疫性疾患の誘引となり得るか? -自己免疫性膵炎及び原発性胆汁性肝硬変モデルを用いた発症機構の検討-2011

    • Author(s)
      春田郁子、柳沢直子、ミヤケ深雪、加藤秀人、白鳥敬子、八木淳二
    • Organizer
      第21回 Kyoto T cell conference
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] Ercherichia coli induced autoimmune pancreatitis in C57BL/6 mice2011

    • Author(s)
      Naoko Yanagisawa, Ikuko Haruta, Junji Yagi
    • Organizer
      XIII International congress of bacteriology and applied microbiology
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] Is the disregulation of homeostatic inflammation involved in the pathogenesis of innate-immune mediated hepato-biliary-pancreatic autoimmune disease?: Analysis using mice models of primary biliary cirrhosis and autoimmune pancreatitis2011

    • Author(s)
      Ikuko Haruta, Naoko Yanagisawa, Hidehito Kato, Miyuki Omori-Miyake, Hidehiro Ueshiba, Junji Yagi
    • Organizer
      XIII International congress of bacteriology and applied microbiology
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] 自己免疫性膵炎マウスモデルの発症機構に関与する大腸菌構成因子の解明2011

    • Author(s)
      柳沢直子、春田郁子、ミヤケ深雪、白鳥敬子、八木淳二
    • Organizer
      第40回 日本免疫学会総会
    • Place of Presentation
      幕張
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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