{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:24:39Z","timestamp":1787973879003,"version":"build-2784847793"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["91742108,81670019,81800026,81600023"],"award-info":[{"award-number":["91742108,81670019,81800026,81600023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key Research and Development Program of China","award":["2016YFC1304400"],"award-info":[{"award-number":["2016YFC1304400"]}]},{"name":"Hubei Province Natural Science Foundation","award":["2017CFA016"],"award-info":[{"award-number":["2017CFA016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,8]]},"abstract":"<jats:p>The epithelial cell\u2013derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) initiate type 2 inflammation in allergic diseases, including asthma. However, the signaling pathway regulating these cytokines expression remains elusive. Since microRNAs are pivotal regulators of gene expression, we profiled microRNA expression in bronchial epithelial brushings from type 2\u2013low and type 2\u2013high asthma patients. miR-206 was the most highly expressed epithelial microRNA in type 2\u2013high asthma relative to type 2\u2013low asthma but was downregulated in both subsets compared with healthy controls. CD39, an ectonucleotidase degrading ATP, was a target of miR-206 and upregulated in asthma. Allergen-induced acute extracellular ATP accumulation led to miR-206 downregulation and CD39 upregulation in human bronchial epithelial cells, forming a feedback loop to eliminate excessive ATP. Airway ATP levels were markedly elevated and strongly correlated with IL-25 and TSLP expression in asthma patients. Intriguingly, airway miR-206 antagonism increased Cd39 expression; reduced ATP accumulation; suppressed IL-25, IL-33, and Tslp expression and group 2 innate lymphoid cell expansion; and alleviated type 2 inflammation in a mouse model of allergic airway inflammation. In contrast, airway miR-206 overexpression had opposite effects. Overall, epithelial miR-206 upregulates airway IL-25 and TSLP expression by targeting the CD39\u2013extracellular ATP axis, which represents a potentially novel therapeutic target in type 2\u2013high asthma.<\/jats:p>","DOI":"10.1172\/jci.insight.148103","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T12:03:06Z","timestamp":1620129786000},"source":"Crossref","is-referenced-by-count":24,"title":["Epithelial miR-206 targets CD39\/extracellular ATP to upregulate airway IL-25 and TSLP in type 2\u2013high asthma"],"prefix":"10.1172","volume":"6","author":[{"given":"Kan","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."},{"name":"Key Laboratory of Respiratory Diseases, National Health Commission of People\u2019s Republic of China, and National Clinical Research 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