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IRF-4 is associated with the development of granulomas in autoimmune disease

Research Project

Project/Area Number 23591442
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionFukushima Medical University

Principal Investigator

SEKINE Hideharu  福島県立医科大学, 医学部, 教授 (40363759)

Co-Investigator(Renkei-kenkyūsha) YUI Katsuyuki  長崎大学, 医学部, 教授 (90274638)
HONMA Kiri  長崎大学, 医学部, 准教授 (70307940)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsIRF4 / IRF1 / 自己免疫 / 肉芽腫 / 国際情報交換 / アメリカ / IRF-4 / IRF-1
Research Abstract

Mechanisms of granuloma formation in autoimmune diseases is unknown. We found that transcription factor IRF4-deficient lupus-prone MRL/lpr mice develop granulomas with Langhans giant cells in multiple organs including lung. We also found that IRF4-deficient MRL/lpr mice had increased numbers of IFN-g-producing Th1 cells with elevated levels of serum IFN-g. While, transcription factor IRF1-deficient MRL/lpr mice had increased numbers of IL-4-producing Th2 cells and granulomas with foreign body giant cells in their lung. Our data indicate that transcription factor IRF4 and IRF1 play important roles to maintain Th1/Th2-cell/cytokine balance, and defect of these transcription factors causes development of granulomatous lesions in multiple organs.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (37 results)

All 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 5 results) Presentation (20 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Role of complement in a murine model of peanut-induced anaphylaxis2013

    • Author(s)
      Kodama T, Sekine H, Takahashi M, Iwaki D, Machida T, Kanno K, Ishida Y, Endo Y, and Fujita T
    • Journal Title

      Immunobiology

      Volume: 218 Pages: 844-850

    • Related Report
      2013 Final Research Report
  • [Journal Article] Comment on "Mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required for alternative pathway function"2013

    • Author(s)
      Takahashi M, Sekine H, Endo Y, and Fujita T
    • Journal Title

      J Immunol

      Volume: 190 Pages: 2477-2477

    • Related Report
      2013 Final Research Report
  • [Journal Article] The role of MASP-1/3 in complement activation2013

    • Author(s)
      Sekine H, Takahashi M, Iwaki D, and Fujita T
    • Journal Title

      Adv Exp Med Biol

      Volume: 735 Pages: 41-53

    • Related Report
      2013 Final Research Report
  • [Journal Article] 補体の異常値と疾患2013

    • Author(s)
      関根英治,町田豪,坂本夏美,高橋実
    • Journal Title

      福島医学雑誌

      Volume: 63 Pages: 93-107

    • NAID

      40019766693

    • Related Report
      2013 Final Research Report
  • [Journal Article] Aged IRF-4-deficient lupus-prone MRL/lpr mice show peripheral B-cell deficiency with elevated serum IFN-γ levels and increased expression of IFN-γ-receptor-1 on B cells.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, and Hideharu Sekine
    • Journal Title

      Front Immunol

      Volume: N/A

    • DOI

      10.3389/conf.fimmu.2013.02.00861

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of IRF-1 accelerates development of tubulointerstitial nephritis and pulmonary granulomas with predominant Th2 polarity in lupus-prone MRL/lpr mice.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Eiji Suzuki, Xian Zhang, Christopher M. Reilly, Gary S. Gilkeson, and Hideharu Sekine
    • Journal Title

      Front Immunol

      Volume: N/A

    • DOI

      10.3389/conf.fimmu.2013.02.00862

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of complement in a murine model of peanut-induced anaphylaxis.2013

    • Author(s)
      Kodama T1, Sekine H, Takahashi M, Iwaki D, Machida T, Kanno K, Ishida Y, Endo Y, Fujita T.
    • Journal Title

      Immunobiology

      Volume: 218 Issue: 6 Pages: 844-850

    • DOI

      10.1016/j.imbio.2012.10.003

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comment on "mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required for alternative pathway function"2013

    • Author(s)
      Takahashi M, Sekine H, Endo Y, Fujita T.
    • Journal Title

      J Immunol.

      Volume: 190 Issue: 6 Pages: 2477-2477

    • DOI

      10.4049/jimmunol.1390002

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of MASP-1/3 in complement activation.2013

    • Author(s)
      Hideharu Sekine, Minoru Takahashi, Daisuke Iwaki, and Teizo Fujita
    • Journal Title

      Adv Exp Med Biol.

      Volume: 735 Pages: 41-53

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 補体の異常値と疾患.2013

    • Author(s)
      関根英治, 町田豪, 坂本夏美, 高橋実
    • Journal Title

      福島医学雑誌

      Volume: 63 Pages: 93-107

    • NAID

      40019766693

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The Role of MASP-1/3 in Complement Activation.2013

    • Author(s)
      Sekine H, Takahashi M, Iwaki D, Fujita T.
    • Journal Title

      Adv Exp Med Biol

      Volume: 735 Pages: 41-53

    • Related Report
      2012 Research-status Report
  • [Journal Article] Association of the toll-like receptor 9 gene polymorphisms with Behcet's disease in a Japanese population2012

    • Author(s)
      Sakamoto N, Sekine H, Kobayashi H, Sato Y, Ohira H
    • Journal Title

      Fukushima J Med Sci

      Volume: 58 Pages: 127-135

    • NAID

      130002566785

    • Related Report
      2013 Final Research Report
  • [Journal Article] Association of the toll-like receptor 9 gene polymorphisms with Behcet's disease in a Japanese population.2012

    • Author(s)
      Sakamoto N, Sekine H, Kobayashi H, Sato Y, Ohira H.
    • Journal Title

      Fukushima J Med Sci

      Volume: 58 Pages: 127-135

    • NAID

      130002566785

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The benefit of targeted and selective inhibition of the alternative complement pathway for modulating autoimmunity and renal disease in MRL/lpr mice2011

    • Author(s)
      Sekine H, Kinser TT, Qiao F, Martinez E, Paulling E, Ruiz P, Gilkeson GS, and Tomlinson S
    • Journal Title

      Arthritis Rheum

      Volume: 63 Pages: 1076-1085

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Journal Article] The dual role of complement in the progression of renal disease in NZB/W F1 mice and alternative pathway inhibition2011

    • Author(s)
      Sekine H, Ruiz P, Gilkeson GS, and Tomlinson S
    • Journal Title

      Mol Immunol

      Volume: 49 Pages: 317-323

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] Lack of IRF-1 accelerates development of tubulointerstitial nephritis and pulmonary granulomas with predominant Th2 polarity in lupus-prone MRL/lpr mice2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Eiji Suzuki, Xian Zhang, Christopher M. Reilly, Gary S. Gilkeson, and Hideharu Sekine
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2013-08-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Aged IRF-4- deficient lupus-prone MRL/lpr mice show peripheral B-cell deficiency with elevated serum IFN-γlevels and increased expression of IFN-γ-receptor-1 on B cells2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, and Hideharu Sekine
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2013-08-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Lupus-prone MRL/lpr mice express IFN-γ-receptor-1 abundantly on peripheral B cells that is responsible for peripheral B-cell survival/maintenance and autoantibody production.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, and Hideharu Sekine
    • Organizer
      5th International Conference on “B cells and Autoimmunity”
    • Place of Presentation
      Como Lake, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] Aged IRF-4-deficient lupus-prone MRL/lpr mice show peripheral B-cell deficiency with elevated serum IFN-γ levels and increased expression of IFN-γ-receptor-1 on B cells.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, and Hideharu Sekine
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lack of IRF-1 accelerates development of tubulointerstitial nephritis and pulmonary granulomas with predominant Th2 polarity in lupus-prone MRL/lpr mice.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Eiji Suzuki, Xiang Zhang, Christopher Reilly, Gary Gilkeson, and Hideharu Sekine
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] Masp-1/3 deficient MRL/lpr mice lack the alternative complement pathway activation and are protected from development of lupus-like glomerulonephritis.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Teizo Fujita, Minoru Takahashi, and Hideharu Sekine
    • Organizer
      2013-Annual Scientific Meeting of the American College of Rheumatology (ACR)
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] IFN-γ-receptor-1 is expressed abundantly on splenic B cells of MRL/lpr mice and is involved in peripheral B-cell survival/maintenance and autoantibody production.2013

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, and Hideharu Sekine
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉, 幕張メッセ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lack of interferon regulatory factor-1 accelerates development of interstitial nephritis, renal vasculitis, and pulmonary granulomas with predominant Th2 polarity in lupus-prone MRL/lpr mice2012

    • Author(s)
      Takeshi Machida, Natsumi Sakamoto, Eiji Suzuki, Xian Zhang, Christopher Reilly, Gary S. Gilkeson, and Hideharu Sekine
    • Organizer
      第41回日本免疫学会総会・学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2012-12-07
    • Related Report
      2013 Final Research Report
  • [Presentation] IRF-1 deficient lupus-prone MRL/lpr mice show reduced glomerulonephritis but develop severe interstitial nephritis, renal vasculitis and pulmonary granulomas with propensity for Th2 polarity2012

    • Author(s)
      Hideharu Sekine, Takeshi Machida, Natsumi Sakamoto, Eiji Suzuki, Xian Zhang, Christopher Reilly, and Gary S. Gilkeson
    • Organizer
      The 76th Annual Meeting of the American College of Rheumatology
    • Place of Presentation
      Washington, DC, USA
    • Year and Date
      2012-11-12
    • Related Report
      2013 Final Research Report
  • [Presentation] IRF-1 Deficient Lupus-Prone MRL/Lpr Mice Show Reduced Glomerulonephritis but Develop Severe Interstitial Nephritis, Renal Vasculitis and Pulmonary Granulomas with Propensity for Th2 Polarity.2012

    • Author(s)
      Sekine H, Machida T, Sakamoto N, Suzuki E, Zhang X, Reilly C, Gilkeson GS
    • Organizer
      American College of Rheumatology (ACR) Scientific Meeting, 2012
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of complement in a murine model of peanut-induced anaphylaxis.2012

    • Author(s)
      Kodama T, Endo Y, Takahashi M, Iwaki D, Machida T, Fujita T, and Sekine H
    • Organizer
      XXIV International Complement Workshop
    • Place of Presentation
      Hania, Greece
    • Related Report
      2012 Research-status Report
  • [Presentation] Lack of interferon regulatory factor-1 accelerates development of interstitial nephritis, renal vasculitis, and pulmonary granulomas with predominant Th2 polarity in lupus-prone MRL/lpr mice.2012

    • Author(s)
      Machida T, Sakamoto N, Suzuki E, Zhang X, Reilly C, Gilkeson GS, Sekine H
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] IRF-4欠損MRL/lprマウスはTh1過剰応答を起こし複数の組織に肉芽腫生病変を発症する2011

    • Author(s)
      町田豪,本間季里,松山俊文,由井克之, Ruiz Phil,藤田禎三,Gilkeson Gary,関根英治
    • Organizer
      第40回日本免疫学会総会・学術集会
    • Place of Presentation
      幕張,千葉
    • Year and Date
      2011-11-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Interferon regulatory factor-4 deficient lupus-prone MRL/lpr mice show strong propensity for Th1 polarity and develop granulomatous lesions in multiple organs2011

    • Author(s)
      Hideharu Sekine, Takeshi Machida, Eiji Suzuki, Christopher Reilly, Xian Zhang, Phil Ruiz and Gary S. Gilkeson
    • Organizer
      The 75th Annual Meeting of the American College of Rheumatology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2011-11-06
    • Related Report
      2013 Final Research Report
  • [Presentation] The benefit of targeted and selective inhibition of the alternative complement pathway for modulating autoimmunity and renal disease in murine models of systemic lupus erythematosus2011

    • Author(s)
      Hideharu Sekine, Phil Ruiz, Gary S. Gilkeson, and Stephen Tomlinson
    • Organizer
      The 5th Complement Workshop
    • Place of Presentation
      Ixia, Rhodes, Greece
    • Year and Date
      2011-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] IRF-4はMRL/lprマウスのB細胞分化・成熟に必須である2011

    • Author(s)
      町田豪,山内直人,関根英治
    • Organizer
      基礎合同セミナーポスター発表会2011
    • Place of Presentation
      福島
    • Related Report
      2013 Final Research Report
  • [Presentation] Interferon regulatory factor-4 deficient lupus-prone MRL/Lpr mice show strong propensity for Th1 polarity and develop granulomatous lesions in multiple organs2011

    • Author(s)
      Sekine H, Machida T, Suzuki E, Reilly C, Zhang X, Ruiz P, Gilkeson GS
    • Organizer
      American College of Rheumatology (ACR) Scientific Meeting
    • Place of Presentation
      Chicago, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] The benefit of targeted and selective inhibition of the alternative complement pathway for modulating autoimmunity and renal disease in murine models of systemic lupus erythematosus2011

    • Author(s)
      Sekine H, Ruiz P, Gilkeson GS, Tomlinson S
    • Organizer
      5th International Complement Therapeutics Conference
    • Place of Presentation
      Rhodes, Greece
    • Related Report
      2011 Research-status Report
  • [Presentation] IRF-4 deficient lupus-prone MRL/lpr mice develop granulomatous lesions in multiple organs with strong propensity for Th1 polarity2011

    • Author(s)
      Takeshi Machida, Kiri Honma, Toshifumi Matsuyama, Katsuyuki Yui, Phil Ruiz, Teizo Fujita, Gary Gilkeson, and Hideharu Sekine
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉 幕張メッセ
    • Related Report
      2011 Research-status Report
  • [Presentation] 転写因子IRF-4欠損SLEモデルマウスにおける CD4陽性T細胞の動態と、疾患表現型の変化

    • Author(s)
      関根 英治
    • Organizer
      第七回自己免疫疾患研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] 免疫複合体の可溶化とクリアランス,In補体への招待2011

    • Author(s)
      関根英治(大井洋之,木下タロウ,松下操編)
    • Publisher
      メジカルビュー社
    • Related Report
      2013 Final Research Report
  • [Book] 補体の検査法と意義,In臨床検査増刊号・ここまでわかった自己免疫疾患2011

    • Author(s)
      関根英治(宮坂信之)
    • Publisher
      医学書院
    • Related Report
      2013 Final Research Report

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

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