A new therapeutic strategy against systemic sclerosis targeting skin immunity

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19473
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Tohoku University
• Principal Investigator: ASANO YOSHIHIDE 東北大学, 医学系研究科, 教授 (60313029)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 全身性強皮症 / 皮膚免疫 / 制御性T細胞 / 核酸医薬 / 臓器線維化

Outline of Final Research Achievements

The etiology of systemic sclerosis (SSc) still remains unknown, but we hypothesized that skin immunity may regulate multi-organ fibrosis based on the following facts: organ fibrosis begins in the skin and the skin is the largest immune organ of the human body in contact with the outside world. Our previous study suggested that RALDH1 activity of dermal DCs in SSc lesional skin is decreased and induction of iTregs is suppressed. The present study showed that suppression of RALDH1 expression in the skin of BLM-treated mice increased fibrosis not only in the skin but also in the lungs　and esophagus. These results suggest that RALDH1 activity in the skin regulates skin stiffness in SSc and may also regulate pulmonary and esophageal fibrosis. We are currently working to identify microRNAs that induce RALDH1 expression.

Free Research Field

全身性強皮症

Academic Significance and Societal Importance of the Research Achievements

近年、アレルギー疾患においては皮膚免疫の重要性が示されており、アトピー性皮膚炎が喘息や花粉症、食物アレルギーの発症につながるアレルギーマーチという概念が確立されている。本研究成果は、全身性強皮症に代表される膠原病においても皮膚免疫が多臓器障害を制御している可能性を示唆している。申請者は既に全身性エリテマトーデスにおいて皮膚免疫がその発症に深く関わることを明らかにしているが、これらの研究成果は皮膚免疫が全身性免疫疾患の治療戦略の標的となり得ることを示唆している。皮膚は外用薬や貼付薬で容易にアクセス可能であり、新規治療薬開発の観点からも学術的・社会的意義の高い研究成果である。