biostudies-literatureWiesner DLNCATS NIH HHSNIAID NIH HHSCouncil on Ocean Affairs Science and Technology, California State UniversityNational Heart, Lung, and Blood InstituteNHLBI NIH HHSNational Institutes of HealthHartwell FoundationNIDDK NIH HHSCystic Fibrosis FoundationCharles H. Hood FoundationNCI NIH HHSNorth Carolina Biotechnology CenterNIH HHSNIGMS NIH HHSNational Science Foundation614-628.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC7305569biostudies-literatureUnknown27(4)Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club cCell host & microbeClub Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation.PMC7305569R37 AI035681R01 AI136529UL1 TR002373T32 HL007899T32 AI055397S10 OD018202P50 GM64598P30 CA014520PO1 HL70381T32 AI007635T32 GM008692P01 HL070831DBI-9977525R01AI136529T32 HL1162751S100OD018202-01T32 HL07899R01 AI130411R01 AI040996DBI-0520825UL1 TR000427R33 DK070297MOU19G0R01 AI035681P50 GM064598Ober CBrockman-Schneider RAFreeman MKlein BSKeller NPMou HGern JEEsnault SJWiesner DLWarner TJackson DJJarjour NNVyas JMMerkhofer RMNiu MEvans MDFeldman MBKujoth GCfalseClub Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation.Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club c2020-01-01T00:00:00Z2020 Apr2026-05-01T16:30:54.482Z2022-02-09T12:51:57.315ZS-EPMC73055693213095410.1016/j.chom.2020.02.006