Dopamine receptor D2 antagonization normalizes the profibrotic macrophage-endothelial crosstalk in the liver

Fibrosis in the liver is a main histological determinant of non-alcoholic steatohepatitis (NASH), a disease paralleling a worldwide surge in metabolic syndrome. Our study demonstrates that myeloid-specific YAP deficiency attenuates liver fibrosis after chronic liver injury via boosting type I interferon. Dopamine receptor D2 (DRD2) antagonization selectively blocks YAP in macrophages and thwarts liver fibrosis in both rodent and large animal models. Overall design: liver nonparenchymal cells scRNA sequence of fibrosis model wild type (WT) and yap1flox/floxlyz2cre mice