A small-molecule enhancer of STAT1 affects herpes simplex keratitis prognosis by mediating plasmacytoid dendritic cells migration through CXCR3/CXCL10.

Herpes simplex keratitis (HSK) is a prevalent infectious corneal disorder. This study aims to explore the role of plasmacytoid dendritic cells (pDCs) in HSK, an area that remains underexplored. The investigation centers on the effects of a STAT1 transcription enhancer, 2-NP, on pDCs and its underlying mechanisms. Our findings revealed that 2-NP treatment significantly reduced corneal opacity and neovascularization in a mouse HSK model. This intervention increased CXCR3 expression on the cell membrane, promoting pDC migration to the cornea via the CXCR3/CXCL10 axis. Additionally, it triggered STAT1 phosphorylation, enhancing IFN-α production, which in turn activated the JAK1/STAT1 signaling pathway. These results uncover a novel molecular mechanism by which the STAT1 transcriptional enhancer drives pDC migration to inflamed corneas, presenting a new therapeutic strategy for HSK.