Elucidation of the pathogenesis of localized dermatosis by analysis of gene clusters that determine the site specificity of human skin

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: YAMAMOTO YUICHI 琉球大学, 医学(系)研究科(研究院), 客員研究員 (00363672)
• Co-Investigator(Kenkyū-buntansha): 高橋 健造 琉球大学, 医学(系)研究科(研究院), 教授 (80291425)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 掌蹠 / 躯幹 / 角化 / 自然免疫 / トランスクリプトーム

Outline of Final Research Achievements

The purpose of this study was to understand the keratinization process, innate immunity and acquired immunity in the sole and the trunk skin by differential gene expression. We found that Langerhans cells were decreased in palmoplantar skin, while antimicrobial peptides were expressed 10 times higher in plantar than in trunk skin. Regional differences in the expression of these antimicrobial peptides and species may explain the differences in the skin microbiome by region.
As for KLKs, which define the thickness of stratum corneum, and SPINKs and SERPINs, which inhibit KLKs, the expression of KLKs was generally decreased in plantar skin compared with that in trunk skin, while the expression of SPINK5 was similar between trunk and plantar skin. SPINK6, 7 and 9, which specifically inhibit KLK5, were highly expressed in plantar skin but not in trunk skin.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

KLKとSPINK、SERPIN同位体群の発現量の違いにより掌蹠の角層に特徴的な稠密な角層を構築すると考えられる。ネザートン症候群の原因遺伝子であるSPINK5は、体幹と掌蹠で発現に差はないが、SPINK6, 7, 9は体幹皮膚には発現しておらず足底皮膚に特異的に高発現していた。この同位体発現により、ネザートン症候群患者が掌蹠には角層剥離の症状を呈さないのかと考えた。長島型掌蹠角化症では角化は掌蹠縁をこえて手背・足背やアキレス腱に及ぶ。SERPINB7自体は体幹の皮膚にも発現しており、SERPINB7遺伝子の発現分布のみでは、掌蹠に限局する過角化の病態は説明できない。