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

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 樹状細胞 / サイトカイン / 上皮細胞 / 炎症 / 免疫疾患 / サイトカイントカイン

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.

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。

Research Products

• [Journal Article] Pivotal Role of IL-22 Binding Protein in the Epithelial Autoregulation of Interleukin-22 Signaling in the Control of Skin Inflammation (2018)
  • Author(s): Tomohiro Fukaya, Takehito Fukui, Tomofumi Uto, Hideaki Takagi, Junta Nasu, Noriaki, Miyanaga, Keiichi Arimura, Takeshi Nakamura, Haruhiko Koseki, Narantsog Choijookhuu, Yoshitaka Hishikawa, Katsuaki Sato
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 1-13
  • DOI: 10.3389/fimmu.2018.01418
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Pivotal role of IL-22BP in the epithelial autoregulation of IL-22 signaling in the control of skin inflammation (2018)
  • Author(s): 深谷知宏、福井丈仁、宇都倫史、高木秀明、奈須遵太、宮永宜明、佐藤克明
  • Organizer: 第47回日本免疫学会学術集会
• [Remarks] 宮崎大学医学部医学科感染症学講座免疫学分野ホームページ
  • URL: http://www.med.miyazaki-u.ac.jp/meneki/