Analysis of the influence of immunosuppressive drugs on human sweat glands: a search for a reason why corticosteroid is effective for anhidrosis?

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17360
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyorin University
• Principal Investigator: Shimoda Yurie 杏林大学, 医学部, 助教 (50774204)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 汗腺 / 細胞培養 / 無汗症

Outline of Final Research Achievements

The aim of this study is to elucidate the influence of immunosuppressive drugs, represented by corticosteroid using in vitro expanded human sweat gland cells. Isolated human sweat gland explants successfully gave rise to culture cell which could be propagated and passaged, while partially maintaining sweat gland marker expression levels. Using these cells, global gene expression analysis was conducted by microarrays to find that corticosteroid up-regulated genes involved in the responses to external stimuli and stress in the cells examined. In parallel with these analysis, digital image analyses for quantitative evaluation of the outcomes of sweat test and immunohistochemical assessment of human sweat gland were invented to conduct a correlation analysis to link clinical effectiveness of corticosteroid for anhidrosis and changes in microarray analyses. The current study set the basis for in-depth dissection of mode-of-action of immunosuppressive drugs for the treatment of anhidrosis.

Free Research Field

発汗障害

Academic Significance and Societal Importance of the Research Achievements

無汗症には経験的にステロイドの全身投与が有効な場合もあるが、その病態や薬剤の作用機序などについては未だ明らかではない。本研究では、ヒト汗腺から部分的ではあるが特性を維持した培養細胞を継代培養する技術を確立し、ステロイドなどの免疫抑制剤が汗腺に与える影響についてマイクロアレイをはじめとする網羅的遺伝子解析技術を用いて検討しうることを示すとともに、こうした基礎医学的手法を用いて得た定量的な知見を臨床所見、臨床検体を用いた解析の結果と橋渡しするための方法論を確立した。本研究で得られた知見は、その希少性などから困難とされてきた無汗症の病態解明及び治療開発に向けた技術的基盤の一助になると考えた。