• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the mechanisms of orang fibrosis using patients with IgG4-related disease and their mouse models

Research Project

Project/Area Number 19H03854
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionKyushu University

Principal Investigator

Maehara Takashi  九州大学, 歯学研究院, 助教 (10637333)

Co-Investigator(Kenkyū-buntansha) 新納 宏昭  九州大学, 医学研究院, 教授 (20380636)
森山 雅文  九州大学, 大学病院, 助教 (20452774)
山元 英崇  九州大学, 大学病院, 准教授 (30404073)
中村 誠司  九州大学, 歯学研究院, 教授 (60189040)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
KeywordsIgG4関連疾患 / 全身性強皮症 / 線維化 / マクロファージ / 細胞障害性T細胞 / T細胞 / B細胞 / IgG4-RD / CD4+CTL / CD8+CTL / シェーグレン症候群 / Tリンパ球 / Bリンパ球 / 線維芽細胞 / CD4+
Outline of Research at the Start

現在では世界で注目されている IgG4 関連疾患(IgG4-RD)は本邦から提唱された疾患である。全身の種々の臓器に病変を生じ罹患臓器への T 細胞および B 細胞の浸潤に伴う不可逆性の臓器線維化ならびに特異な免疫グロブリンのクラススイッチ(主に IgG4)を特徴とする特異な疾患である。未だこの疾患に特徴的な臓器線維化の分子機構は不明であり有効な治療法が無い難病である。本研究では IgG4-RD に特異的な免疫異常と臓器線維化の分子機序を明らかにし、新規治療法開発の基盤を築くことを目指す。

Outline of Final Research Achievements

IgG4-related diseases, which were first proposed in Japan and are now attracting worldwide attention, are diseases characterized by lesions in organs throughout the body and irreversible organ fibrosis associated with infiltration of T and B cells into the affected organs. However, the molecular mechanism of organ fibrosis that characterizes this disease is still unknown, and the disease is intractable with no effective treatment. Because fibrosis is irreversible and leads to deterioration of organ function, the development of novel therapeutic methods is required. In this study, we identified lymphocytes involved in organ fibrosis and investigated their relationship with characteristic macrophages involved in organ fibrosis.

Academic Significance and Societal Importance of the Research Achievements

IgG4-RD は本邦から提唱された疾患で、涙腺・唾液腺炎を初めとして自己免疫性膵炎、後腹膜線維症、硬化性胆管炎、間質性肺炎などの多くの病変を生じ、活性化した T 細胞と B 細胞の組織浸潤や特徴的なマクロファージの浸潤に伴う不可逆性の臓器線維化を特徴とする全身疾患である。この臓器線維化のメカニズムを明らかにすることができれば、新たな治療標的分子を明らかにすることができる。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 8 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (3 results)

  • [Int'l Joint Research] Ragon 研究所/マサチューセッツ総合病院(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Ragon Institute(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] CD163+ M2 Macrophages Promote Fibrosis in IgG4-Related Disease Via Toll-like Receptor 7/Interleukin-1 Receptor-Associated Kinase 4/NF-κB Signaling2022

    • Author(s)
      Chinju Akira、Moriyama Masafumi、Kakizoe‐Ishiguro Noriko、Chen Hu、Miyahara Yuka、Haque A. S. M. Rafiul、Furusho Katsuhiro、Sakamoto Mizuki、Kai Kazuki、Kibe Kotono、Hatakeyama‐Furukawa Sachiko、Ito‐Ohta Miho、Maehara Takashi、Nakamura Seiji
    • Journal Title

      Arthritis & Rheumatology

      Volume: in press Issue: 5 Pages: 1-10

    • DOI

      10.1002/art.42043

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutralizing anti IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease2022

    • Author(s)
      Jarrell Justin A.、Baker Matthew C.、Perugino Cory A.、Liu Hang、Bloom Michelle S.、Maehara Takashi、Wong Heidi H.、Lanz Tobias V.、Adamska Julia Z.、Kongpachith Sarah、Sokolove Jeremy、Stone John H.、Pillai Shiv S.、Robinson William H.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 149 Issue: 1 Pages: 358-368

    • DOI

      10.1016/j.jaci.2021.05.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease.2022

    • Author(s)
      Ryusuke M,Takashi M, Yuka M, Rusako K, Ryuichi A, Naoki K, Atsushi D, Cory A.P., Emanuel DT, Takako S, Yasuharu S, Hidetaka Y, Tamotsu K, John HS, Shiv P, Seiji N.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: in press Issue: 2 Pages: 440-455.e17

    • DOI

      10.1016/j.jaci.2022.03.034

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mer tyrosine kinase as a possible link between resolution of inflammation and tissue fibrosis in IgG4-related disease2021

    • Author(s)
      Rovati Lucrezia、Kaneko Naoki、Pedica Federica、Monno Antonella、Maehara Takashi、Perugino Cory、Lanzillotta Marco、Pecetta Simone、Stone John H、Doglioni Claudio、Manfredi Angelo A、Pillai Shiv、Della-Torre Emanuel
    • Journal Title

      Rheumatology

      Volume: 60 Issue: 10 Pages: 4929-4941

    • DOI

      10.1093/rheumatology/keab096

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CD4+ and CD8+ cytotoxic T lymphocytes may induce mesenchymal cell apoptosis in IgG4-related disease2021

    • Author(s)
      Perugino Cory A., Moriyama Masafumi(28名中24番目), et al.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 147 Issue: 1 Pages: 368-382

    • DOI

      10.1016/j.jaci.2020.05.022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis2020

    • Author(s)
      Maehara Takashi、Kaneko Naoki、Perugino Cory A.、Mattoo Hamid、Kers, Jesper、Allard-Chamard Hugues、Mahajan Vinay S.、Liu Hang、Murphy Samuel J.H.、Ghebremichael Musie、Fox David、Payne Aimee S.、Lafyatis Robert、Stone John H.、Khanna Dinesh、Pillai Shiv
    • Journal Title

      Journal of Clinical Investigation

      Volume: 130 Issue: 5 Pages: 2451-2464

    • DOI

      10.1172/jci131700

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of circulating SLAMF7+Tfh1 cells with IgG4 levels in patients with IgG4-related disease.2020

    • Author(s)
      Higashioka K, Ota Y, Maehara T, et. al.
    • Journal Title

      BMC Immunol.

      Volume: 21 Issue: 1 Pages: 31-31

    • DOI

      10.1186/s12865-020-00361-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease2020

    • Author(s)
      Della-Torre Emanuel、Rigamonti Elena、Perugino Cory、Baghai-Sain Simona、Sun Na、Kaneko Naoki、Maehara Takashi、Rovati Lucrezia、Ponzoni Maurilio、Milani Raffaella、Lanzillotta Marco、Mahajan Vinay、Mattoo Hamid、Molineris Ivan、Deshpande Vikram、Stone John H.、Falconi Massimo、Manfredi Angelo A.、Pillai Shiv
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 145 Issue: 3 Pages: 968-981.e14

    • DOI

      10.1016/j.jaci.2019.07.004

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Review of a novel disease entity, immunoglobulin G4-related disease2020

    • Author(s)
      Maehara Takashi、Moriyama Masafumi、Nakamura Seiji
    • Journal Title

      Journal of the Korean Association of Oral and Maxillofacial Surgeons

      Volume: 46 Issue: 1 Pages: 3-3

    • DOI

      10.5125/jkaoms.2020.46.1.3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Tissue-infiltrating immune cells contribute to understanding the pathogenesis of Kimura disease: A case report2019

    • Author(s)
      Maehara T, Munemura R, Shimizu M, Kakizoe N, Kaneko N, Murakami Y, Moriyama M, Kiyoshima T, Kawano S, Nakamura S.
    • Journal Title

      Medicine

      Volume: in press Issue: 50 Pages: e18300-e18300

    • DOI

      10.1097/md.0000000000018300

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activated M2 macrophage contributes to the pathogenesis of IgG4-related disease via TLR7/IL-33 signalin.2019

    • Author(s)
      Ishiguro N, Moriyama M, Furusho K, Furukawa S, Shibata T, Murakami Y, Chinju A, Haque ASMR, Gion Y, Ohta M, Maehara T, Tanaka A, Yamauchi M, Sakamoto M, Mochizuki K, Ono Y, Hayashida JN, Sato Y, Kiyoshima T, Yamamoto H, Miyake K, Nakamura S
    • Journal Title

      Arthritis Rheumatol.

      Volume: Jan;72(1) Issue: 1 Pages: 166-178

    • DOI

      10.1002/art.41052

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathogenesis of IgG4-related disease: a critical review.2019

    • Author(s)
      Maehara T, Moriyama M, Nakamura S.
    • Journal Title

      Odontology

      Volume: 107 Pages: 127-132

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production.2019

    • Author(s)
      Haque ASMR, Moriyama M, Kubota K, Ishiguro N, Sakamoto M, Chinju A, Mochizuki K, Sakamoto T, Kaneko N, Munemura R, Maehara T, Tanaka A, Hayashida JN, Kawano S, Kiyoshima T, Nakamura S.
    • Journal Title

      Sci Rep.

      Volume: Oct 10;9(1) Issue: 1 Pages: 14611-14611

    • DOI

      10.1038/s41598-019-51149-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features and mechanistic insights regarding IgG4-related dacryoadenitis and sialoadenitis: a review.2019

    • Author(s)
      Maehara T, Pillai S, Stone JH, Nakamura S.
    • Journal Title

      Int J Oral Maxillofac Surg

      Volume: 印刷中 Issue: 7 Pages: 908-916

    • DOI

      10.1016/j.ijom.2019.01.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] IgG4-related disease: Immunological insights into the pathogenesis2021

    • Author(s)
      Takashi Maehara
    • Organizer
      23rd Asia-Pacific League of Associations for Rheumatology Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Single-cell transcriptome analysis identifies clonally-expanded infiltrating CD4+ and CD8+ cytotoxic T lymphocytes in IgG4-related disease2021

    • Author(s)
      Takashi Maehara
    • Organizer
      4th International symposium of IgG4-related disease
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IgG4関連疾患の病態形成におけるClonalに増殖したCD4+CTLとCD8+CTL細胞の病態への関与2020

    • Author(s)
      前原隆、金子直樹、宗村龍祐、村上祐香、中村誠司
    • Organizer
      第74回 日本口腔科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] IgG4関連疾患の臓器線維化と炎症の免疫学的病態解明2020

    • Author(s)
      前原隆、宗村龍祐、金子直樹、村上祐香、中村誠司
    • Organizer
      第65回 日本口腔外科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A novel disease entity, IgG4-related disease: Immunological insights into the pathogenesis2019

    • Author(s)
      Takashi Maehara, Seiji Nakamura
    • Organizer
      The 9th Japan-Thailand-Korea Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] IgG4関連疾患の病態と治療へ向けて2019

    • Author(s)
      前原隆
    • Organizer
      第28回 日本シェーグレン症候群学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 次世代シークエンサー解析が紐解く,全身性強皮症の病態における Clonal に増殖した CD4+T 細胞 -国際共同研究-2019

    • Author(s)
      前原隆、PERUGINO Cory、金子直樹、MATTOO Hamid、宗村龍祐、山元英崇、PILLAI Shiv、中村誠司
    • Organizer
      第73回NPO 法人日本口腔科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A novel disease discovered and established in Japan: IgG4-related disease2019

    • Author(s)
      Takashi Maehara
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] IgG4関連疾患の代替療法2020

    • Author(s)
      前原隆、中村誠司
    • Total Pages
      5
    • Publisher
      Current Therapy
    • Related Report
      2020 Annual Research Report
  • [Book] IgG4関連疾患の病態2020

    • Author(s)
      前原隆、宗村龍祐、村上祐香、中村誠司
    • Total Pages
      4
    • Publisher
      臨床免疫・アレルギー科
    • Related Report
      2020 Annual Research Report
  • [Book] 新規疾患概念;IgG4関連疾患の免疫学的特徴から臓器線維化と炎症の病態解明へ向けて2020

    • Author(s)
      前原隆、宗村龍祐、村上祐香、中村誠司
    • Total Pages
      4
    • Publisher
      アレルギーの臨床
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi