Differential regulation of the transcriptomic and secretomic landscape of sensor and effector funtions of human airway epithelial cells

Protein secretion upon TLR, TNFR1 and IFNGR ligation in the human airways are considered to be central to the orchestration of pulmonary inflammatory and immune responses. In this study, we compared the gene expression and protein secretion profile in response to specific stimulation of all expressed TLRs and in further comparison to TNFR1 and IFNGR in primary human airway epithelial cells (AEC). Beyond 22 cytokines, we observed the receptor-induced regulation of 571 genes and 1012 secreted proteins. Further analysis revealed high similarities between the transcriptional TLR sensor and TNFR1 effector responses. However, secretome to transcriptome comparisons showed a broad receptor-dependent release of proteins that were not transcriptionally regulated. Many of these proteins exhibited an exosomal annotation with associations e.g. to antigen presentation and wound-healing or were identified as secretable proteins related to immune responses. Thus, we show a hitherto unrecognized scope of receptor induced responses in airway epithelium, which involves several additional functions for immune response, exosomal communication and tissue homeostasis.