Development of novel strategies for treating systemic sclerosis focusing on circulating monocytes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nippon Medical School
• Principal Investigator: KUWANA Masataka 日本医科大学, 大学院医学研究科, 教授 (50245479)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 強皮症 / 単球 / マクロファージ / 肺高血圧症 / 肺線維症 / 動物モデル

Outline of Final Research Achievements

Systemic sclerosis or scleroderma is characterized by excessive fibrosis of the skin and other internal organs, and still remains an intractable condition based on lack of any effective therapeutics. In this study, we have found that macrophages are recruited to the affected organs before development of apparent fibrosis in a mouse model for systemic sclerosis. Macrophages detected in the affected organs are primarily fibrogenic M2 macrophages, which are upregulated under a control of transcription factor Fra-1. Gene expression of Fra-1 is also increased in circulating monocytes derived from patients with systemic sclerosis, compared with those from healthy controls. In summary, our results together indicate that upregulated expression of Fra-1 promotes differentiation of monocytes into M2 macrophages, which are recruited to the skin and other organs affected and promote excessive fibrosis.

Free Research Field

膠原病学