Department of Dermatology, King Fahd University Hospital, Alkhobar, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Clin Exp Immunol. 2024 Mar 12;216(1):80-88. doi: 10.1093/cei/uxae003.
T-cell recruitment to skin tissues is essential for inflammation in different cutaneous diseases; however, the mechanisms by which these T cells access the skin remain unclear. High endothelial venules expressing peripheral node address in (PNAd), an L-selectin ligand, are located in secondary lymphoid organs and are responsible for increasing T-cell influx into the lymphoid tissues. They are also found in non-lymphoid tissues during inflammation. However, their presence in different common inflammatory cutaneous diseases and their correlation with T-cell infiltration remain unclear. Herein, we explored the mechanisms underlying the access of T cells to the skin by investigating the presence of PNAd-expressing vessels in different cutaneous diseases, and its correlation with T cells' presence. Skin sections of 43 patients with different diseases were subjected to immunohistochemical and immunofluorescence staining to examine the presence of PNAd-expressing vessels in the dermis. The correlation of the percentage of these vessels in the dermis of these patients with the severity/grade of CD3+ T-cell infiltration was assessed. PNAd-expressing vessels were commonly found in the skin of patients with different inflammatory diseases. A high percentage of these vessels in the dermis was associated with increased severity of CD3+ T-cell infiltration (P < 0.05). Additionally, CD3+ T cells were found both around the PNAd-expressing vessels and within the vessel lumen. PNAd-expressing vessels in cutaneous inflammatory diseases, characterized by CD3+ T-cell infiltration, could be a crucial entry point for T cells into the skin. Thus, selective targeting of these vessels could be beneficial in cutaneous inflammatory disease treatment.
T 细胞向皮肤组织的募集对于不同皮肤疾病的炎症反应至关重要;然而,这些 T 细胞进入皮肤的机制仍不清楚。表达外周淋巴结地址素(PNAd)的高内皮静脉位于次级淋巴器官中,负责增加 T 细胞向淋巴组织的流入。它们也存在于非淋巴组织的炎症过程中。然而,它们在不同常见炎症性皮肤疾病中的存在及其与 T 细胞浸润的相关性尚不清楚。在此,我们通过研究不同皮肤疾病中 PNAd 表达血管的存在及其与 T 细胞存在的相关性,探讨 T 细胞进入皮肤的机制。对 43 例不同疾病患者的皮肤切片进行免疫组织化学和免疫荧光染色,以检查真皮中 PNAd 表达血管的存在。评估这些患者真皮中这些血管的百分比与 CD3+T 细胞浸润的严重程度/分级的相关性。PNAd 表达血管常见于不同炎症性疾病患者的皮肤中。真皮中这些血管的高百分比与 CD3+T 细胞浸润的严重程度增加相关(P<0.05)。此外,CD3+T 细胞既存在于 PNAd 表达血管周围,也存在于血管管腔中。在以 CD3+T 细胞浸润为特征的皮肤炎症性疾病中,PNAd 表达血管可能是 T 细胞进入皮肤的关键入口。因此,选择性靶向这些血管可能有益于皮肤炎症性疾病的治疗。