Analysis of the role of S100A8/A9 and its novel receptors in chronic inflammation in atopic dermatitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860899
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Tokyo Medical University
• Principal Investigator: YAMAMOTO Mami 東京医科大学, 医学部, 助教 (60421062)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: アトピー性皮膚炎 / S100A8/A9

Outline of Final Research Achievements

Previously, we reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer (EMMPRIN), an S100A9 receptor. Therefore, we assumed that S100A8/A9 plays an important role in the chronic inflammation that arises from barrier disruption in atopic dermatitis. In this study, we identified neuroplastin-β (NPTNβ) as a novel S100A8 receptor. The S100A8-NPTNβ signal activated keratinocyte proliferation, while the S100A9-EMMPRIN signaling pathway induced skin inflammation. NPTNβ and EMMPRIN formed homodimers and a heterodimer. S100A8 and S100A9 were strongly expressed and co-localized with these receptors in the lesional skin of atopic dermatitis. These results indicate that NPTNβ and EMMPRIN form a functional heterodimeric receptor for S100A8/A9 and play a critical role in atopic dermatitis.

Free Research Field

皮膚科学