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

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

Affiliations

  • 1 Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Aier Eye Hospital of Wuhan University, Wuhan, China. Electronic address: ophywj@whu.edu.cn.
  • 3 Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: ophyyn@163.com.
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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