Vascular endothelial cells (VECs) that line the interiors of blood vessels participate in physiological and inflammatory processes. All skin cell types express the aryl hydrocarbon receptor (AhR), which is involved in the pathogenesis of psoriasis. However, the role of the cutaneous VEC AhR in the pathogenesis of psoriasis remains elusive. In the present study, we found that AhR protein expression and activation were downregulated in psoriatic VECs. Furthermore, cutaneous VEC-specific AhR-knockout (AhRcVECs-KO) mice were established. Using imiquimod and IL-23-induced psoriasis models, we found that skin inflammation was exacerbated with excessive neutrophil recruitment in AhRcVECs-KO mice. Furthermore, neutrophil neutralization alleviates exacerbated inflammation in imiquimod-treated AhRcVECs-KO mice. In addition, cutaneous VECs in AhRcVECs-KO mice exhibited increased dilation and activation compared with those in control mice. Finally, AhR-deficient microvascular endothelial cells stimulated by proinflammatory cytokines showed increased ICAM-1 expression in vivo and in vitro, which may have facilitated neutrophil recruitment. In summary, our study demonstrates that AhR in dermal VECs restricts psoriasis development by negatively regulating neutrophil recruitment, thereby providing insight into the pathogenesis of psoriasis.

中文翻译：

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皮肤血管内皮细胞中的芳烃受体通过负调节中性粒细胞的募集来限制牛皮癣的发展。

衬在血管内部的血管内皮细胞（VEC）参与生理和炎症过程。所有类型的皮肤细胞均表达芳基烃受体（AhR），这与牛皮癣的发病机理有关。然而，皮肤VEC AhR在牛皮癣发病机理中的作用仍然难以捉摸。在本研究中，我们发现银屑病VECs中的AhR蛋白表达和激活被下调。此外，建立了皮肤VEC特异性AhR基因敲除（AhRcVECs-KO）小鼠。使用咪喹莫特和IL-23诱导的牛皮癣模型，我们发现在AhRcVECs-KO小鼠中，过度嗜中性粒细胞募集会加剧皮肤炎症。此外，中性粒细胞中和减轻了咪喹莫特治疗的AhRcVECs-KO小鼠的炎症恶化。此外，与对照小鼠相比，AhRcVECs-KO小鼠中的皮肤VEC表现出增加的扩张和激活。最后，促炎细胞因子刺激的AhR缺陷型微血管内皮细胞在体内和体外显示ICAM-1表达增加，这可能促进了嗜中性白细胞的募集。总而言之，我们的研究表明，真皮VEC中的AhR通过负调节中性粒细胞的募集来限制牛皮癣的发展，从而为牛皮癣的发病机理提供见识。