Elucidation of pathophysiology of inflammatory skin disease from the viewpoint of neutrophil function and establishment of its treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kagoshima University
• Principal Investigator: Higashi Yuko 鹿児島大学, 医歯学域医学系, 准教授 (00381179)
• Co-Investigator(Kenkyū-buntansha): 山口 宗一 鹿児島大学, 医歯学域医学系, 准教授 (20325814)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: microRNA / 好中球 / 乾癬 / 顆粒球吸着除去療法

Outline of Final Research Achievements

Microarray analysis of microRNAs (miRNAs) was performed using sera before and after granulocyte and monocyte adsorption apheresis for patients with neutrophilic skin disease. Several miRNAs significantly increased in patients compared to controls. The expression of these miRNAs decreased after apheresis, suggesting that these miRNAs might be involved in the pathogenesis of neutrophilic skin decrease. When the human promyelocytic leukemia cell lines, including HL60, were stimulated with all-trans retinoic acid, the cells were morphologically changed to neutrophil-like cells. The expression of selected miRNAs increased during the differentiation of these neutrophil-like cells. Moreover, the role of these miRNAs in regulating proliferation of cultured keratinocytes were proved. These data suggested that these miRNAs could be used as neutrophilic skin disease marker.

Free Research Field

好中球性皮膚疾患、乾癬

Academic Significance and Societal Importance of the Research Achievements

好中球性皮膚疾患のほとんどが原因不明の疾患であり、既存の治療に抵抗を示す難治例も多い。本研究で、好中球性皮膚疾患で高値を示すmiRNAを探りだし、これらが治療により減少することを見出した。また、好中球の活性化とともにmiRNAの発現も増加することが示唆された。これらは好中球性皮膚疾患の病勢マーカーとして用いられる可能性とmiRNAを標的とする治療法の開発へつながる新たな展開も伺える成果であると考える。