Elucidation of the mechanisms of orang fibrosis using patients with IgG4-related disease and their mouse models
| Project/Area Number |
19H03854
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| 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)
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| Keywords | IgG4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+ |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(27 results)
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[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.
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Journal Title
Journal of Allergy and Clinical Immunology
Volume: in press
Issue: 2
Pages: 440-455.e17
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Journal of Allergy and Clinical Immunology
Volume: 145
Issue: 3
Pages: 968-981.e14
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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
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Journal Title
Arthritis Rheumatol.
Volume: Jan;72(1)
Issue: 1
Pages: 166-178
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Sci Rep.
Volume: Oct 10;9(1)
Issue: 1
Pages: 14611-14611
DOI
Related Report
Peer Reviewed / Open Access
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