Role of PD-L1 in Regulatory T Cell-Mediated Suppression of Corneal Neovascularization.

IF 3.6 2区 医学 Q1 PATHOLOGY
Shima Dehghani, Manuel Chacon, Katayoon Forouzanfar, Seokjoo Lee, Akitomo Narimatsu, Rohan Bir Singh, Aytan Musayeva, Francesca Kahale, Sonia Anchouche, Neda Heydarian, Shilpy Bhullar, Thomas H Dohlman, Yihe Chen, Tomas Blanco, Reza Dana
{"title":"Role of PD-L1 in Regulatory T Cell-Mediated Suppression of Corneal Neovascularization.","authors":"Shima Dehghani, Manuel Chacon, Katayoon Forouzanfar, Seokjoo Lee, Akitomo Narimatsu, Rohan Bir Singh, Aytan Musayeva, Francesca Kahale, Sonia Anchouche, Neda Heydarian, Shilpy Bhullar, Thomas H Dohlman, Yihe Chen, Tomas Blanco, Reza Dana","doi":"10.1016/j.ajpath.2025.08.008","DOIUrl":null,"url":null,"abstract":"<p><p>Corneal neovascularization (NV) leads to inflammation and fibrosis, thereby compromising visual acuity and corneal graft survival. Despite existing antiangiogenic therapies, clinical outcomes remain suboptimal. This study explores the antiangiogenic potential of regulatory T cells (Tregs) through programmed death-ligand 1 (PD-L1). In vitro tube formation assays were performed by co-culturing MS1 endothelial cells with Tregs. In addition, murine corneal suture-induced NV and high-risk corneal transplantation models were used to evaluate the effects of subconjunctival Treg injections in vivo. Wild-type (WT) Tregs inhibited endothelial tube formation, whereas PD-L1<sup>-/-</sup> Tregs failed to exert this effect. Blocking B7-1 on MS1 cells attenuated the inhibitory effect of WT Tregs, indicating a PD-L1-B7-1 interaction as a key mechanism. Furthermore, vascular endothelial growth factor A expression in MS1 cells was significantly reduced on co-culturing with WT Tregs, a response that was absent with PD-L1<sup>-/-</sup> Tregs. In vivo, subconjunctival Treg injections significantly reduced corneal NV in both corneal suture-induced NV and high-risk corneal transplantation models, and this effect was lost on blocking PD-L1. These results show that PD-L1 expressed by Tregs plays a pivotal role in suppressing corneal angiogenesis, acting through a contact-dependent mechanism through B7-1, leading to down-regulation of vascular endothelial growth factor A, highlighting the function of PD-L1 in Treg modulation of corneal angiogenesis.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2025.08.008","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Corneal neovascularization (NV) leads to inflammation and fibrosis, thereby compromising visual acuity and corneal graft survival. Despite existing antiangiogenic therapies, clinical outcomes remain suboptimal. This study explores the antiangiogenic potential of regulatory T cells (Tregs) through programmed death-ligand 1 (PD-L1). In vitro tube formation assays were performed by co-culturing MS1 endothelial cells with Tregs. In addition, murine corneal suture-induced NV and high-risk corneal transplantation models were used to evaluate the effects of subconjunctival Treg injections in vivo. Wild-type (WT) Tregs inhibited endothelial tube formation, whereas PD-L1-/- Tregs failed to exert this effect. Blocking B7-1 on MS1 cells attenuated the inhibitory effect of WT Tregs, indicating a PD-L1-B7-1 interaction as a key mechanism. Furthermore, vascular endothelial growth factor A expression in MS1 cells was significantly reduced on co-culturing with WT Tregs, a response that was absent with PD-L1-/- Tregs. In vivo, subconjunctival Treg injections significantly reduced corneal NV in both corneal suture-induced NV and high-risk corneal transplantation models, and this effect was lost on blocking PD-L1. These results show that PD-L1 expressed by Tregs plays a pivotal role in suppressing corneal angiogenesis, acting through a contact-dependent mechanism through B7-1, leading to down-regulation of vascular endothelial growth factor A, highlighting the function of PD-L1 in Treg modulation of corneal angiogenesis.

PD-L1在调节性T细胞介导的角膜新生血管抑制中的作用。
角膜新生血管(NV)导致炎症和纤维化,从而影响视力和角膜移植存活。尽管现有的抗血管生成疗法,临床结果仍然不理想。本研究探讨了调节性T细胞(Treg)通过程序性死亡配体1 (PD-L1)的抗血管生成潜能。MS-1内皮细胞与Treg共培养,进行体外成管实验。此外,采用小鼠角膜缝合诱导的NV和高风险角膜移植模型来评估结膜下Treg注射在体内的作用。野生型(WT) Treg抑制内皮管的形成,而PD-L1-/- Treg不能发挥这种作用。阻断B7-1对MS-1细胞的抑制作用减弱了WT Treg的抑制作用,表明PD-L1-B7-1相互作用是其关键机制。此外,与WT Treg共培养时,MS-1细胞中的VEGF-A表达显著降低,而PD-L1-/- Treg则没有这种反应。在体内,结膜下Treg注射可显著降低角膜缝线诱导NV和高风险角膜移植模型的角膜NV,而这种作用在阻断PD-L1后消失。这些结果表明,Treg表达的PD-L1在抑制角膜血管生成中起关键作用,通过B7-1的接触依赖机制,导致VEGF-A下调,突出了PD-L1在Treg调节角膜血管生成中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信