Clarification of the mechanism and treatment of down-regulated innate immunity in atopic dermatitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K09745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kagawa University
• Principal Investigator: Nakai Kozo 香川大学, 医学部附属病院, 講師 (40363204)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: アトピー性皮膚炎

Outline of Final Research Achievements

Macrophages are central to innate immunity and become polarized towards the M1 or M2 states upon activation by immunostimulants. We examined whether macrophages are activated in the skin of a model for IL-17A-induced chronic atopic dermatitis-like skin inflammation. LPS and IL-17A independently increased the expression levels of iNOS, CX3CR1, CD206, phospho-STAT1 and phospho-STAT3 proteins in the skin of B6 mice, and the effects of LPS was not altered by IL-17A. The expression levels of these proteins were increased in the skin of atopic mice. IL-17A neutralization decreased the expressions of CD206 and phospho-STAT3 proteins in the skin of atopic mice, suggesting that macrophages to change from the M2 to the M1 state in the skin of these mice. These results suggest that IL-17A is involved in the activation of macrophages that are in the process of adopting the heterogeneous profiles of both the M1 and M2 states.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎の病態について、表皮のバリア形成異常や炎症性サイトカイン産生過剰などについて明らかになってきた。我々はこれまで皮膚における活性酸素の生理学的・病理学的役割について基礎・臨床研究を行ってきた。アトピー性皮膚炎患者尿中の活性酸素代謝物が増加していること、アトピー性皮膚炎モデルマウスにおいて活性酸素が表皮バリア機構を形成する細胞接着因子の発現を調節すること、抗酸化剤アセチルシステインがAD患者の皮膚バリア機構を改善することなどを報告している。そして、これら皮膚の活性酸素発生にはマクロファージが最も重要な役割を果たしていることが今回の研究でわかってきた。