| Project/Area Number |
25293242
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Sato Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Yoshihide 東京大学, 医学部附属病院, 准教授 (60313029)
KADONO Takafumi 聖マリアンナ医科大学, 病院, 准教授 (80292910)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 全身性強皮症 / B細胞 / Fli1 / 免疫異常 / 血管障害 / 線維化 / CD19 / ブレオマイシン / 皮膚硬化 / 自己免疫 / ＣＤ１９ / Ｆｌｉ１ |
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| Outline of Final Research Achievements |
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by initial vascular injury and resultant tissue fibrosis with autoimmune background. In addition to autoantibody production, B cells have been shown to be directly involved in the development of SSc. Since our studies have proved a critical role of Fli1 deficiency in the induction of SSc-like phenotypes in dermal fibroblasts, endothelial cells, and macrophages, we here investigated the role of Fli1-deficeint B cells in SSc pathogenesis. When we generated B cell-specific Fli1 knockout mice (Fli1flox/flox;Cd19-Cre+/-), B cells were abnormally activated and these mice spontaneously developed vascular changes resembling SSc vasculopathy, subsequently exhibiting tissue fibrosis of the skin and lung. These results indicate that Fli1 deficiency induces SSc-like phenotypes in B cells as well as other cell types, integrating the expression of fibrosis-related gene programs into the development of SSc.
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