Analysis of the role of IL-22 binding protein in the regulatory mechanism for chronic skin inflammation

• Project/Area Number: 17K15732
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: University of Miyazaki
• Principal Investigator: Fukaya Tomohiro 宮崎大学, 医学部, 助教 (20624323)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 免疫寛容 / 自己免疫 / 免疫学

Outline of Final Research Achievements

Il22ra2－/－ mice exhibited a more severe IMQ-induced psoriatic dermatitis than WT mice. Furthermore, Il22ra2－/－ mice showed enhanced epidermal infiltration of inflammatory leukocytes and higher transcriptional expression of cytokines and chemokines, as well as epithelial inflammation-related molecules, in psoriatic lesions. Although keratinocytes showed increased proliferation and aberrant differentiation upon stimulation with IL-22, IL-22BP entirely inhibited the IL-22 mediated changes in the functionality of keratinocytes. Thus, our findings suggest that IL-22BP has a critical role in the regulation of IL-22 signaling in keratinocytes to prevent chronic inflammatory skin diseases.

Academic Significance and Societal Importance of the Research Achievements

これまでに未知であった皮膚炎症慢性化病態の成立機構におけるIL-22シグナル調節機構の役割および“IL-22BP機能”に着眼した分子基盤を解明した。さらに、非感染性慢性炎症性皮膚免疫疾患の成立における新たな概念の提唱により、当該領域の発展へ貢献した。

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] Early life antibiotic-driven gut dysbiosis promotes the breakdown of oral tolerance mediated through the dysregulation of dendritic cells (2019)
  • 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、西川陽太郎、佐藤克明
  • Organizer: 第48回日本免疫学会総会
• [Presentation] Requirement of gut mucosal plasmacytoid dendritic cells for establishing oral tolerance to prevent undesirable allergic disorders (2019)
  • Author(s): 宇都倫史、高木秀明、深谷知宏、奈須遵太、福井丈仁、宮永宜明、西川陽太郎、佐藤克明
  • Organizer: 第48回日本免疫学会総会
• [Presentation] Essential role of submandibular lymph node conventional dendritic cells in the protective effect of sublingual immunotherapy on allergic asthma (2019)
  • Author(s): 高木秀明、宮永宜明、宇都倫史、深谷知宏、奈須遵太、福井丈仁、西川陽太郎、佐藤克明
  • Organizer: 第48回日本免疫学会総会
• [Presentation] Pivotal role of CD103 expressed on conventional dendritic cells in the development of psoriasiform dermatitis through the regulation of cutaneous inflammation (2019)
  • Author(s): 福井丈仁、深谷知宏、宇都倫史、高木秀明、奈須遵太、宮永宜明、西川陽太郎、佐藤克明
  • Organizer: 第48回日本免疫学会総会
• [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
• [Presentation] Crucial role of CD103 in the development of psoriasiform dermatitis through the regulation of cutaneous inflammation (2018)
  • Author(s): 福井丈仁, 深谷知宏, 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
• [Presentation] Crucial role of conventional dendritic cells in the protective effect of sublingual immunotherapy (SLIT) on allergic disorders (2018)
  • Author(s): 高木秀明, 宮永宜明, 宇都倫史, 深谷知宏, 奈須遵太, 福井丈仁, 佐藤克明
  • Organizer: 第４7回日本免疫学会学術集会
• [Presentation] Tolerogenic function of conventional dendritic cells in the protective effect of sublingual immunotherapy (SLIT ) on allergic disorders (2018)
  • Author(s): 宮永宜明, 高木秀明, 宇都倫史, 深谷知宏, 奈須遵太, 福井丈仁, 佐藤克明
  • Organizer: 第４7回日本免疫学会学術集会
• [Presentation] Critical role of plasmacytoid dendritic cells in establishing oral tolerance leading to abortive allergic sensitization (2018)
  • Author(s): 宇都倫史, 高木秀明, 深谷知宏, 奈須遵太, 福井丈仁, 宮永宜明, 佐藤克明
  • Organizer: 第４7回日本免疫学会学術集会
• [Presentation] Critical role of IL-22 binding protein in the control of skin inflammation (2017)
  • 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, 有村慶一, 中村雄, 佐藤克明
  • Organizer: 第４6回日本免疫学会学術集会
• [Presentation] Critical role of plasmacytoid dendritic cells in the induction of oral tolerance for the control of allergic sensitization (2017)
  • Author(s): 宇都倫史, 高木秀明, 深谷知宏, 奈須遵太, 福井丈仁, 宮永宜明, 有村慶一, 中村雄, 佐藤克明
  • Organizer: 第４6回日本免疫学会学術集会
• [Presentation] Tolerogenesis of gastrointestinal plasmacytoid dendritic cells impacts the induction of oral tolerance (2017)
  • Author(s): 高木秀明, 宇都倫史, 深谷知宏, 奈須遵太, 福井丈仁, 宮永宜明, 有村慶一, 中村雄, 佐藤克明
  • Organizer: 第４6回日本免疫学会学術集会