Elucidation of pathological significance of IgG4 using a novel mouse model
| Project/Area Number |
19K22537
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
Baba Yoshihiro 九州大学, 生体防御医学研究所, 教授 (20415269)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | IgG4 / B細胞 |
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| Outline of Research at the Start |
IgG4関連疾患は様々な臓器の肥厚性病変を認める全身性疾患であり、血中IgG4の高値と、罹患部のIgG4陽性プラズマ細胞の浸潤および線維化を特徴とする。自己免疫機序の関与が想定されているが、未だに原因は不明であり、疾患発症機序の解明と新規治療法の開発が急がれる。本研究では、新規マウスモデルを樹立し、免疫グロブリンIgG4産生B細胞の応答とIgG4抗体の疾患への関与を解明することにより、IgG4関連疾患およびアレルギー疾患病態の理解を目指す。
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| Outline of Final Research Achievements |
IgG4-related disease is characterized by high blood IgG4 antibody levels and fibrosis. In addition, IgG4 has been shown to suppress allergies. Although the relationship between IgG4 and allergic diseases is suspected, the details are unknown. A major reason for the lack of progress in IgG4 research is the absence of IgG4 in mice. Therefore, we gnerated a new mouse that produces human IgG4. We showed that B cell differentiation of this mouse was normal. In addition, IgG4 production was observed by immunization. Thus, the newly created IgG4-producing mouse may be a useful tool for verifying the role of IgG4 in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で作成した新規ヒトIgG4産生マウスは、これまで不可能だったIgG4陽性B細胞のin vivoでの活性化や分化、ならびにIgG4抗体の疾患制御の役割を検証することが可能となり、IgG4の病理的意義を直接的に調べることができる。よって、IgG4関連疾患およびアレルギー疾患の理解と予測、さらには、治療の選択に貢献できると考えられる。また、謎の多いIgG4の機能という、基礎免疫学の研究領域の発展に大きく貢献することが期待される。
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity2020
Author(s)
Tanaka, S. Ise, W. Inoue, T. Ito, A. Ono, C. Shima, Y. Sakakibara, S. Nakayama, M. Fujii, K. Miura, I. Sharif, J. Koseki, H. Koni, P. A. Raman, I. Li, Q. Z. Kubo, M. Fujiki, K. Nakato, R. Shirahige, K. Araki, H. Miura, F. Ito, T. Kawakami, E. Baba, Y. Kurosaki, T.
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Journal Title
Nat. Immunol.
Volume: 21
Pages: 950-961
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells2019
Author(s)
Usui R, Yabe D, Fauzi M, Goto H, Botagarova A, Tokumoto S, Tatsuoka H, Tahara Y, Kobayashi S, Manebe T, Baba Y, Kurosaki T, Herrera PL, Ogura M, Nagashima K, Inagaki N
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Journal Title
Sci. Rep.
Volume: 9
Pages: 15562-15562
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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