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

  • Int Immunopharmacol. 2025 Feb 6:147:113959. doi: 10.1016/j.intimp.2024.113959.
Yujin Wang  1 ,  Jiewen Mao  1 ,  Kuiliang Yang  1 ,  Qian Deng  1 ,  Yuelan Gao  1 ,  Yulin Yan  1 ,  Zixian Yang  1 ,  Yuyu Cong  1 ,  Shanshan Wan  1 ,  Wanju Yang  2 ,  Yanning Yang  3
Affiliations
  • 1. Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2. Aier Eye Hospital of Wuhan University, Wuhan, China. Electronic address: [email protected].
  • 3. Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: [email protected].
PMID: 39755108 DOI: 10.1016/j.intimp.2024.113959
Abstract

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.

Keywords
CXCR3; Herpes simplex keratitis (HSK); JAK1/STAT1 signaling pathway; Plasmacytoid Dendritic Cells (pDCs).
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