Mechanism of the ILC2 activation in bronchial asthma regulated by deltaNp63-related epimmunome

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21249
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology; Respiratory organ internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: KUBO Terufumi 札幌医科大学, 医学部, 助教 (90580019)
• Research Collaborator: TSUJIWAKI Mitsuhiro ; HIROHASHI Yoshihiko ; TSUKAHARA Tomohide ; KANASEKI Takayuki ; NAKATSUGAWA Munehide ; HASEGAWA Tadashi ; TORIGOE Toshihiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 気管支喘息 / 気管支上皮細胞 / deltaNp63 / プロテアーゼ / サイトカイン

Outline of Final Research Achievements

ΔNp63-positive basal epithelial cells were covered with differentiated ΔNp63-negative cells in healthy bronchial tissue; however, ΔNp63-positive cells were directly exposed to the bronchial lumen due to severe epithelial shedding in the asthmatic airway. ΔNp63 regulated bronchial apoptosis in response to Toll-like receptor 3 stimulation. Expression of ΔNp63 was modulated by stimulation with the certain type of protease signal. On the other hand, ΔNp63 controlled the transcriptional expression and protein release of some epithelium-derived proinflammatory cytokines and endogenous protease inhibitors.

Free Research Field

機能病理学

Academic Significance and Societal Importance of the Research Achievements

我々の検討によって気管支上皮細胞が発現するdeltaNp63はウイルス感染に対する気管支上皮細胞の反応を制御しうることが示された。また、deltaNp63の発現を制御するプロテアーゼはハウスダストに含まれるダニに含まれている。つまり、気管支上皮細胞の振る舞いを制御するdeltaNp63は、気管支喘息の増悪の主たる原因となるウイルス感染とハウスダスト曝露を結びつける因子となっている可能性が示唆された。