Type I and II interferons drive inflammation through STAT1 in murine macrophage activation syndrome.
Macrophage activation syndrome (MAS) exemplifies a cytokine storm syndrome by liver inflammation whereby interferon (IFN)-?, which activates the JAK1/2-STAT1 pathway, is being a key driver cytokine. Ruxolitinib, a JAK1/2 inhibitor, has shown promising results in treating MAS patients, however the exact mechanism responsible for disease remission is unclear. One of the mediators inhibited by Ruxolitinib is STAT1, but its role in MAS pathogenesis remains unexplored. In this study, we explored the hepatic immune landscape of MAS and the role of STAT1 herein, using a Toll-like receptor (TLR)9-induced murine model of MAS. Cellular indexing of transcriptomes and epitopes-single cell RNA sequencing (CITE-seq) was performed on the immune compartment of the livers from wild-type (WT) and STAT1 knockout (KO) mice in naive conditions and upon induction of MAS. Overall design: We performed CITE-seq on the immune compartment of the liver from PBS-injected and CpG-injected C57BL/6 WT and C57BL/6 STAT1 KO. Of each condition, a pool of cells (n = 4-8 mice, 1:1 female:male) was stained with fluoresence-activated cell sorting (FACS) antibodies and CITE-seq antibodies. Sorted CD45+ liver cells (69,000) were enriched with CD3-CD19-CD45+F4/80+ cells (1,000 cells) and subjected to sequencing (10x Genomics).