2015 Fiscal Year Final Research Report
The role of transcription factor Fli1 in macrophage polarization in patients with systemic sclerosis
| Project/Area Number |
25461663
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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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| Research Field |
Dermatology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 全身性強皮症 / 免疫異常 / 炎症 / 血管障害 / 線維化 / マクロファージ |
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| Outline of Final Research Achievements |
Systemic sclerosis (SSc) is characterized by three pathological features, including immune abnormalities/inflammation, vasculopathy, and fibrosis. A series of our studies demonstrated that Fli1 deficiency contributes to the development of vasculopathy and fibrosis of SSc, but the role of Fli1 deficiency in immune abnormalities/inflammation still remains unknown. Therefore, to address this issue, we here investigated the impact of Fli1 deficiency on myeloid cells. Our results demonstrated the following findings: (i) Fli1 deficiency promotes the differentiation of macrophages into M2 subtype, (ii) myeloid cell-specific Fli1 knockout (Fli1 MyeKO) mice spontaneously develop dermal fibrosis due to endothelial-to-mesenchyaml transition following initial vascular changes, (iii) Fli1 MyeKO mice exhibit Th2/Th17-skewed immune polarization. Taken together, these results indicate that myeloid Fli1 deficiency is involved in the development of the three cardinal pathological features of SSc.
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| Free Research Field |
全身性強皮症
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