2020 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
免疫学
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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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