Analysis of histamine production in sweat glands and its pathogenic roles in skin allergic diseasel

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08302
• 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: Hiroshima University
• Principal Investigator: Takahagi Shunsuke 広島大学, 医系科学研究科(医), 准教授 (40448246)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 汗腺 / ヒスタミン / IL-1 / コリン性蕁麻疹 / アトピー性皮膚炎

Outline of Final Research Achievements

Histidine decarboxylase (HDC) protein, a histamine-producing enzyme, was detected in human and mouse skin sweat glands. Mouse sweat glands also expressed the HDC gene in in-vitro experiments. Culture of sweat glands in extracellular matrix induced histamine production in the culture supernatant and extracellular matrix, indicating that sweat glands have histamine-producing capacity. In addition, genes involved in histamine metabolism and transport were detected in mouse sweat glands, and HDC expression was enhanced by cytokine stimulation. IL-1, a proinflammatory cytokine in sweat, was also produced in mouse sweat glands and its expression was increased via a receptor signaling. This study suggests that mouse sweat glands produce proinflammatory mediators such as histamine and IL-1, and may be associated with the pathogenesis of sweat-related cutaneous allergic diseases.

Free Research Field

皮膚アレルギー疾患

Academic Significance and Societal Importance of the Research Achievements

これまで皮膚アレルギー領域において、ヒスタミン産生細胞として好塩基球と肥満細胞が広く知られてきたが、本研究ではこれらの細胞以外に皮膚に備わる付属器からもヒスタミンが産生されうることを示した。また、汗腺がヒスタミンやIL-1の炎症性メディエータを産生することは、これらのメディエータの産生抑制や阻害は、発汗と関連する皮膚アレルギー疾患の新しい治療薬の開発につながる可能性がある。