Elucidation of mechanism for triggering an onset of atopic dermatitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15022
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Miyai Tomohiro 国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (30812549)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: アトピー性皮膚炎 / トランスクリプトーム / 多臓器連関

Outline of Final Research Achievements

In this study, I focused on the pre-symptomatic phase of atopic dermatitis (AD) and investigated the molecular mechanisms of the onset of the disease. A series of skin-resident cells was sorted from AD model and WT mice at pre-inflammatory periods then subjected to transcriptomic analysis. As a result, most of the cell types showed similar gene expression patterns between AD-model and WT; however, only endothelial cells exhibited different genetic characteristics from early postnatal period. Especially, a hormonal factor gene was ectopically expressed and high level of the protein was detected in the serum of AD-model mice. It was suggested that the inbalance of metabolic/endocrine systems could trigger the onset of local inflammation in the skin.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究において、皮膚局所の現象と全身性の恒常性維持機構との間に強い関連がある可能性が示唆された。実際、アトピー性皮膚炎のリスクファクターとして食生活をはじめとする生活様式の変化に伴う内分泌系異常が挙げられるが、メカニズムはこれまでに明らかになっていない。本研究ではその分子メカニズムの一端として血管内皮細胞由来の新規因子を見いだすことができた。今後、この因子の作用標的や欠損による影響を詳細に解析することで、アトピー性皮膚炎の予防や治療に有用な新規創薬ターゲットとしての応用が期待できる。