CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation

摘要: Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive response associated with allergic inflammation in asthma. Activation of transcription factor NF-κB AECs or secondary mediators via G protein–coupled receptors (GPCRs) is an important component this multifaceted inflammatory cascade. Members caspase recruitment domain family proteins display tissue-specific expression mediate activity numerous stimuli. We have previously shown that domain–containing membrane-associated guanylate kinase protein (CARMA)3 specifically expressed mediates activation these stimulation GPCR agonist lysophosphatidic acid. In study, we demonstrate reduced levels CARMA3 normal human bronchial decreases production proasthmatic a panel asthma-relevant ligands such as acid, adenosine triphosphate, activate GPCRs Alternaria alternata house dust mite. then show genetically modified mice CARMA3-deficient eosinophilia proinflammatory cytokine murine model inflammation. Additionally, impaired dendritic cell maturation lung from Ag processing. conclusion, AEC helps inflammation, critical signaling molecule bridging innate lung.