Comprehensive understanding of p63/p73-dependent deviated state keratinocytes in atopic dermatitis.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16562
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: KUBO Terufumi 札幌医科大学, 医学部, 助教 (90580019)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アトピー性皮膚炎 / サイトカイン / 上皮バリア機能 / p53ファミリー転写因子

Outline of Final Research Achievements

In this study, we aimed to investigate the influence of type 2 inflammatory environment on ΔNp63 expression and AD associated molecules regulated by ΔNp63 in keratinocyte. In healthy skin tissue, we observed inversed expression pattern between ΔNp63 and some barrier related proteins including filaggrin, caspase-14, claudin-1 and claudin-4. ΔNp63 regulated expression of these genes and proteins. In addition, production of IL-1β and IL-33, pro-inflammatory cytokines, were also modulated by ΔNp63. IL-13 interfered ΔNp63 down-regulation during calcium induced keratinocyte differentiation. IL-13 modulated some barrier and inflammation related molecules, which were under regulation of ΔNp63. We propose the IL-13-ΔNp63 axis would integrate two major factors of AD pathogenesis, epidermal barrier dysregulation and increased cytokine production of keratinocyte.

Free Research Field

免疫病理学

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎をはじめとするアトピー・アレルギー性疾患はこの数十年で罹患者数が激増した疾患であり、遺伝的要因に比して生活習慣や環境因子が病態の形成に強く関わっていることは確実である。アトピー性皮膚炎の患者数は非常に多い一方で、抗体医薬が極めて高価であることから、医療経済的にも病態メカニズムの最も上流にあるケラチノサイトの機能を追求し、病態形成の本質に迫ることで予防的方策を確立することが求められている。本研究では、その一端を明らかとすることができたと考える。