循环单核细胞从血流迁移至组织是炎症的早期标志。这一过程在病毒神经侵袭、脑炎和艾滋病毒相关神经认知障碍中发挥着关键作用。单核细胞如何在不干扰不渗透性的情况下局部解压内皮紧密连接相关蛋白（TJAP）以到达中枢神经系统仍然知之甚少。在这里，我们证明人类循环单核细胞表达 TJAP Occludin (OCLN) 以促进通过内皮细胞的轮回。我们发现人单核细胞 OCLN (hmOCLN) 聚集在单核细胞-内皮界面，而 hmOCLN 表达的调节显着影响单核细胞的迁移。此外，我们设计了针对其细胞外环（EL）的 OCLN 衍生肽，并表明处理过的单核细胞的迁移在体外和斑马鱼胚胎中受到抑制，同时保持血管完整性。单核细胞向大脑的迁移是 HIV 神经侵袭的重要过程，我们发现 OCLN 衍生肽显着抑制 HIV 传播到大脑类器官。总之，我们的研究确定了单核细胞 OCLN 在轮回过程中的重要作用，并为制定预防单核细胞浸润和病毒神经侵袭的缓解策略提供了概念验证。© 2024。作者。

Transmigration of circulating monocytes from the bloodstream to tissues represents an early hallmark of inflammation. This process plays a pivotal role during viral neuroinvasion, encephalitis, and HIV-associated neurocognitive disorders. How monocytes locally unzip endothelial tight junction-associated proteins (TJAPs), without perturbing impermeability, to reach the central nervous system remains poorly understood. Here, we show that human circulating monocytes express the TJAP Occludin (OCLN) to promote transmigration through endothelial cells. We found that human monocytic OCLN (hmOCLN) clusters at monocyte-endothelium interface, while modulation of hmOCLN expression significantly impacts monocyte transmigration. Furthermore, we designed OCLN-derived peptides targeting its extracellular loops (EL) and show that transmigration of treated monocytes is inhibited in vitro and in zebrafish embryos, while preserving vascular integrity. Monocyte transmigration toward the brain is an important process for HIV neuroinvasion and we found that the OCLN-derived peptides significantly inhibit HIV dissemination to cerebral organoids. In conclusion, our study identifies an important role for monocytic OCLN during transmigration and provides a proof-of-concept for the development of mitigation strategies to prevent monocyte infiltration and viral neuroinvasion.© 2024. The Author(s).