オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Exophilin-5 regulates allergic airway inflammation by controlling IL-33-mediated Th2 responses.
掲載誌名	正式名：The Journal of clinical investigation
掲載区分	国外
巻・号・頁	130(7),pp.3919-3935
著者・共著者	Katsuhide Okunishi,Hao Wang,Maho Suzukawa,Ray Ishizaki,Eri Kobayashi,Miho Kihara,Takaya Abe,Jun-Ichi Miyazaki,Masafumi Horie,Akira Saito,Hirohisa Saito,Susumu Nakae,Tetsuro Izumi
発行年月	2020/07/01
概要	A common variant in the RAB27A gene in adults was recently found to be associated with the fractional exhaled nitric oxide level, a marker of eosinophilic airway inflammation. The small GTPase Rab27 is known to regulate intracellular vesicle traffic, although its role in allergic responses is unclear. We demonstrated that exophilin-5, a Rab27-binding protein, was predominantly expressed in both of the major IL-33 producers, lung epithelial cells, and the specialized IL-5 and IL-13 producers in the CD44hiCD62LloCXCR3lo pathogenic Th2 cell population in mice. Exophilin-5 deficiency increased stimulant-dependent damage and IL-33 secretion by lung epithelial cells. Moreover, it enhanced IL-5 and IL-13 production in response to TCR and IL-33 stimulation from a specific subset of pathogenic Th2 cells that expresses a high level of IL-33 receptor, which exacerbated allergic airway inflammation in a mouse model of asthma. Mechanistically, exophilin-5 regulates extracellular superoxide release, intracellular ROS production, and phosphoinositide 3-kinase activity by controlling intracellular trafficking of Nox2-containing vesicles, which seems to prevent the overactivation of pathogenic Th2 cells mediated by IL-33. This is the first report to our knowledge to establish the significance of the Rab27-related protein exophilin-5 in the development of allergic airway inflammation, and provides insights into the pathophysiology of asthma.
DOI	10.1172/JCI127839
PMID	32240120