The establishment of animal models of systemic sclerosis based on Fli1 deficiency

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 全身性強皮症 / B細胞 / Fli1 / 免疫異常 / 血管障害 / 線維化

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.

Free Research Field

全身性強皮症