Analysis of the role of IL-22RA2 produced by conventional dendritic cells in the regulatory mechanism for the maintenance of epithelial homeostasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02670
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Sato Katsuaki 宮崎大学, 医学部, 教授 (40301147)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 樹状細胞 / サイトカイン / 上皮細胞 / 炎症 / 免疫疾患

Outline of Final Research Achievements

Il22ra2－/－ mice exhibited more severe progressions of the pathogenesis of psoriatic dermatitis and allergic asthma than WT mice. Furthermore, Il22ra2－/－ mice showed the enhanced inflammation and immune responses as compared with WT mice. On the other hand, IL-22RA2 not only inhibited the IL-22-mediated proliferation and aberrant differentiation of keratinocytes but also protected against the development of psoriatic dermatitis and allergic asthma. Thus, our findings suggest that IL-22RA2 produced by conventional dendritic cells play a critical role in the maintenance of epithelial homeostasis mediated through the regulation of IL-22 signaling in keratinocytes.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまでに不明であった「上皮組織に局在する通常型樹状細胞のIL-22RA2産生」に着目し、上皮組織の恒常性の維持および破綻における“通常型樹状細胞”の意義とその“IL-22RA2”を介する制御機構を初めて証明した。さらに、これまでに未知であった『上皮-免疫系クロストーク』に関する “通常型樹状細胞のIL-22シグナル調節機能”の重要性に基づいた上皮組織恒常性維持における新たな概念の提唱により、当該領域の発展に貢献した。