The role for splenic marginal zone-B cells in autoantibody production in systemic lupus erythematosus
| Project/Area Number |
18K08392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 全身性エリテマトーデス / Marginal zone-B細胞 / 抗dsDNA抗体 / 糸球体腎炎 / MRL/lprマウス / IFN-γ受容体 / TLR7 / SLEモデル / Marginal zone B細胞 / ループス腎炎 / 自己抗体産生 |
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| Outline of Final Research Achievements |
We aimed to determine the involvement of the marginal zone-B (MZ-B) cells, which is isolated from lupus-prone mice, in autoantibody production and development of lupus-like nephritis using lupus-prone MRL/lpr mice. We generated the genetically-modified mice lacking MZ-B cells specifically, designated MZ-B-deficient MRL/lpr mice, and analyzed the mice pathophysiologically. Interestingly, the MZ-B-deficient MRL/lpr mice showed reduced levels of serum anti-dsDNA IgM and IgG3 compared to wild-type littermates, while serum anti-dsDNA IgG levels were similar in the two strains. Furthermore, all individuals of the MZ-B-deficient MRL/lpr mice did not exhibit severe glomerular lesions, while few individuals of the wild-type littermates showed glomerular inflammatory lesions. Taken together, it was strongly suggested that the MZ-B cells of lupus-prone mice are significantly involved in anti-dsDNA antibody production and development of lupus-like glomerulonephritis in lupus-prone MRL/lpr mice.
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| Academic Significance and Societal Importance of the Research Achievements |
代表的な自己免疫疾患である全身性エリテマトーデス(SLE)の病態には、自己抗体を産生するB細胞が重要な役割を担うが、感染防御などに必須なB細胞を温存しながら悪性のB細胞亜集団を抑制する治療戦略が求められている。本研究では学術的位置づけとして、SLEの自己抗体産生と腎炎病態において、末梢B細胞の亜集団の1つである脾臓Marginal zone-B(MZ-B)細胞が関与することを明確に実証した研究である。また社会的位置づけとしては、SLEの治療における免疫抑制という副作用の可能性を低減させる新たな治療戦略の標的としてMZ-B細胞の可能性を提示した研究である。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] A novel complement inhibitor sMAP-FH targeting both the lectin and alternative complement pathways2020
Author(s)
Takasumi M, Omori T, Machida T, Ishida Y, Hayashi M, Suzuki T, Homma Y, Endo Y, Takahashi M, Ohira H, Fujita T, Sekine H
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Journal Title
The FASEB Journal
Volume: 34
Pages: 6598-6612
DOI
Related Report
Peer Reviewed
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[Journal Article] Evidence for Activation of Lectin and Classical Pathway Complement Components in Aqueous Humor of Neovascular Age-Related Macular Degeneration.2020
Author(s)
Omori T, Oguchi Y, Machida T, Kato Y, Ishida Y, Ojima A, Itagaki K, Shintake H, Tomita R, Kasai A, Sugano
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Journal Title
Ophthalmic Research
Volume: 63
Pages: 252-258
DOI
Related Report
Peer Reviewed
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[Journal Article] Cutting Edge: Role of MASP-3 in the physiological activation of factor D of the alternative complement pathway2019
Author(s)
Manabu Hayashi, Takeshi Machida, Yumi Ishida, Yusuke Ogata, Tomoko Omori, Mika Takasumi, Yuichi Endo, Toshiyuki Suzuki, Masayuki Sekimata, Yoshimi Homma, Masahito Ikawa, Hiromasa Ohira, Teizo Fujita, and Hideharu Sekine
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Journal Title
the J Immunol
Volume: 203
Pages: 1411-1416
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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