Single-cell RNA sequencing reveals endothelial STING-dependent immune remodeling in murine metabolic dysfunction-associated steatohepatitis

Here, we investigate how endothelial-intrinsic cGAS-STING signaling integrates metabolic stress signals to reshape adaptive immune responses in metabolic dysfunction-associated steatohepatitis (MASH) at single-cell resolution. We performed single-cell RNA sequencing on liver tissues from endothelial cell-specific Sting knockout mice (Stingfl/fl Cdh5-Cre+) and littermate controls (Stingfl/fl Cdh5-Cre-) subjected to a western diet combined with CCl4 (WD-CCl4) for 12 weeks.

Unbiased cell-type annotation revealed broad immune remodeling following LSEC-STING deletion. Among CD4+ T cells, LSEC-STING deletion resulted in a marked reduction of pathological Th17 cells, accompanied by expansion of regulatory T cells (Tregs), leading to a significantly increased Treg/Th17 ratio. LSEC-STING deletion also reduced exhausted CD8+ T cells while increasing effector CD8+ T cells.