Changes in whole heart gene expression resulting from endothelial TLR2 deletion

We report the application of bulk RNA sequencing for profiling changes in mouse cardiac lysates as a result of changes in innate immunity function. We generated an inducible endothelial cell toll-like receptor 2 knockout and assessed changes in overall gene expression in the absence of pathogen presence. We find that over 200 genes are differentially regulated between the two genotypes that are solely due to the presence of endogenous signaling within these animals. We also show that the genes that are differentially regulated are tied to the immunity function of the endothelium and that removal of toll-like receptor 2 signaling creates a diminished response by the immune system to wound healing and tumor development. Finally, we demonstrate that other immunomodulatory pathways are further affected, suggesting that changes outside of the endothelium are driven by endothelial-toll-like receptor 2 signaling. This study provides a framework for the application of tissue specific knockouts and profiling the role of endothelial as an innate immunity organ. Examination of 2 different genotypes resulting from endothelial cell-specific receptor deletions

本研究报道了利用批量RNA测序（bulk RNA sequencing）分析先天免疫功能改变所致小鼠心脏裂解物的表达谱变化。本研究构建了诱导型内皮细胞Toll样受体2（toll-like receptor 2）敲除模型，并在无病原体存在的条件下评估了整体基因表达的变化。本研究发现，两种基因型小鼠间存在超过200个差异表达基因，该表达差异完全由动物体内的内源信号通路所介导。本研究同时证实，差异表达基因与内皮细胞的免疫功能密切相关；而阻断Toll样受体2信号通路后，免疫系统对创伤愈合与肿瘤发生的应答会出现显著减弱。最后，本研究还证明其他免疫调节通路亦受到进一步影响，这表明内皮细胞以外的生理变化是由内皮Toll样受体2信号通路所驱动的。本研究为组织特异性基因敲除技术的应用，以及解析内皮细胞作为先天免疫器官的功能提供了研究框架。本研究对内皮细胞特异性受体敲除所产生的两种不同基因型样本进行了检测分析。