Protein secretion upon TLR, TNFR1, and IFNGR ligation in the human airways is considered to be central for the orchestration of pulmonary inflammatory and immune responses. In this study, we compared the gene expression and protein secretion profiles in response to specific stimulation of all expressed TLRs and in further comparison to TNFR1 and IFNGR in primary human airway epithelial cells. In addition to 22 cytokines, we observed the receptor-induced regulation of 571 genes and 1,012 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 stimulation-dependent release of proteins that were not transcriptionally regulated. Many of these proteins are annotated to exosomes with associations to, for example, 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, involving several additional functions for the immune response, exosomal communication and tissue homeostasis.

中文翻译：

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人气道上皮细胞传感器和效应器功能的转录组学和分泌组学景观的差异调节。

人类气道中 TLR、TNFR1 和 IFNGR 连接后的蛋白质分泌被认为是协调肺部炎症和免疫反应的核心。在这项研究中，我们比较了基因表达和蛋白质分泌谱，以响应所有表达的 TLR 的特定刺激，并进一步与原代人气道上皮细胞中的 TNFR1 和 IFNGR 进行比较。除了 22 种细胞因子外，我们还观察到受体诱导的 571 种基因和 1,012 种分泌蛋白的调节。进一步的分析揭示了转录 TLR 传感器和 TNFR1 效应器反应之间的高度相似性。然而，分泌组与转录组的比较显示了不受转录调节的广泛的受体刺激依赖性蛋白质释放。这些蛋白质中的许多都被注释到与关联的外泌体，例如，抗原呈递和伤口愈合，或被鉴定为与免疫反应相关的可分泌蛋白。因此，我们展示了气道上皮细胞中受体诱导反应迄今未被认识的范围，涉及免疫反应、外泌体通讯和组织稳态的几种额外功能。