Development of a novel therapy using anti-CX3CL1 antibody in systemic sclerosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09763
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Fukui
• Principal Investigator: Hasegawa Minoru 福井大学, 学術研究院医学系部門, 教授 (50283130)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 強皮症 / CX3CL1 / 新規治療 / 疾患モデル / 線維化

Outline of Final Research Achievements

We investigated the efficacy of anti-mouse CX3CL1 monoclonal antibody (mAb) therapy for skin lesion in two different mouse models of systemic sclerosis (SSc). In the first model, daily subcutaneous bleomycin injections induced skin fibrosis and vascular injury subsequent to inflammation in C57BL/6 mice. However, administration of anti-CX3CL1 mAb or CX3CR1 deficiency significantly inhibited them via reduced dermal infiltration of CX3CR1+ cells. Results of RNA sequencing and qRT-PCR demonstrated that expression of fibrogenic molecules induced by bleomycin injection, was significantly suppressed by anti-CX3CL1 mAb therapy. In the second model, BALB/c newborn mice received subcutaneous injections of TGF-β followed by that of CTGF. However, pretreatment of anti-CX3CL1 mAb significantly inhibited the skin fibrosis and inflammation of this model. No obvious side effects were found. Anti-CX3CL1 mAb therapy could be a novel approach for inflammatory-driven fibrotic skin disorders.

Free Research Field

全身性強皮症