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

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2024.113959

Yujin Wang , Jiewen Mao , Kuiliang Yang , Qian Deng , Yuelan Gao , Yulin Yan , Zixian Yang , Yuyu cong , Shanshan Wan , Wanju Yang , Yanning Yang

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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.

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STAT1的小分子增强子通过CXCR3/CXCL10介导浆细胞样树突状细胞迁移影响单纯疱疹性角膜炎的预后。

单纯疱疹性角膜炎（HSK）是一种常见的感染性角膜疾病。本研究旨在探讨浆细胞样树突状细胞（pDCs）在HSK中的作用，这是一个尚未被充分探索的领域。研究的重点是STAT1转录增强子2-NP对pDCs的影响及其潜在机制。我们的研究结果显示，2-NP治疗可显著降低小鼠HSK模型的角膜混浊和新生血管。这种干预增加了细胞膜上CXCR3的表达，促进pDC通过CXCR3/CXCL10轴向角膜迁移。此外，它触发STAT1磷酸化，增强IFN-α的产生，进而激活JAK1/STAT1信号通路。这些结果揭示了STAT1转录增强子驱动pDC向发炎角膜迁移的一种新的分子机制，为HSK提供了一种新的治疗策略。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.