2021 Fiscal Year Final Research Report
The analysis of SSc pathogenesis utilizing 9 strains of new murine models
| Project/Area Number |
19H03680
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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 53050:Dermatology-related
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| Research Institution | Tohoku University (2021)
The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 全身性強皮症 / 線維化 / 血管障害 / 免疫異常 / 転写因子FLI1 |
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| Outline of Final Research Achievements |
This study was undertaken to investigate the gene program which is driven in the early stage of systemic sclerosis by using animal models with deficiency of Fli1 in various cell types. Major findings were as follows: (i) activated Fli1 +/- B cells produce excessive amount of IL-6 in the presence of macrophages through TLR9 stimulation, (ii) Fli1 deficiency increases the proportion of newly formed B cells, especially B-1a-like B cells, (iii) age-associated B cells are detected in splenic newly formed B cells. These results suggest that Fli1 deficiency is associated with the induction of B cell subset which likely plays a key role in early disease process of systemic sclerosis.
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| Free Research Field |
全身性強皮症
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| Academic Significance and Societal Importance of the Research Achievements |
SScは緩徐に進行する希少疾患ゆえに、発症初期の病態を制御する遺伝子プログラムの同定は極めて困難であり、この点が早期例に対する治療戦略を確立するうえで大きな障害となっている。本研究は、複数のモデルマウスを活用してSScの発症初期の遺伝子プログラムの異常を同定することを目的として立案された。今回の検討により、SScの病態形成の初期に誘導される自己免疫の起源となるB細胞の形質変化が明らかとなった。今回同定したB細胞集団を対象にSSc関連転写因子ネットワークの同定を進め、SScの病態解明と新規治療薬開発の基盤となるデータの構築を進めていく予定である。
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