Endothelial GATA6 deficiency suppresses intracellular TLR3-interferon signaling in HPAECs and promotes interferon response in HPASMCs

The dysregulation of endothelial immune function is a central feature in diseases such as pulmonary arterial hypertension (PAH). In this study, we explored the consequences of GATA6 deficiency in human pulmonary arterial endothelial cells (HPAECs) and its impact on immune response pathways.

We report that siRNA-induced GATA6 deficiency or the GATA inhibitor led to significant downregulation of interferon response genes and a marked reduction in toll-like receptor 3 (TLR3) expression. GATA6 overexpression enhanced the expression of these genes, and TLR3 inhibition abrogated this response. Furthermore, conditioned medium from GATA6-deficient HPAECs upregulated interferon genes in pulmonary artery smooth muscle cells (HPASMCs), indicating a paracrine effect.