PDF(Pubmed)
Abstract：
PD-1/PD-L1 inhibitors have been demonstrated to induce itch in both humans and experimental animals. However, whether the PD-1/PD-L1 pathway is involved in the regulation of chronic psoriatic itch remains unclear. This study aimed to investigate the role of the PD-1/PD-L1 pathway in imiquimod-induced chronic psoriatic itch. The intradermal injection of PD-L1 in the nape of neck significantly alleviated chronic psoriatic itch in imiquimod-treated skin. Additionally, we observed that spontaneous scratching behavior induced by imiquimod disappeared on day 21. Still, intradermal injection of PD-1/PD-L1 inhibitors could induce more spontaneous scratching for over a month, indicating that imiquimod-treated skin remained in an itch sensitization state after the spontaneous scratching behavior disappeared. During this period, there was a significant increase in PD-1 receptor expression in both the imiquimod-treated skin and the spinal dorsal horn in mice, accompanied by significant activation of microglia in the spinal dorsal horn. These findings suggest the potential involvement of the peripheral and central PD-1/PD-L1 pathways in regulating chronic itch and itch sensitization induced by imiquimod.
摘要：
已经证明PD-1/PD-L1抑制剂在人和实验动物中诱导瘙痒。然而,PD-1/PD-L1通路是否参与慢性银屑病瘙痒的调节尚不清楚.本研究旨在探讨PD-1/PD-L1通路在咪喹莫特诱导的慢性银屑病瘙痒中的作用。颈项皮内注射PD-L1可显着减轻咪喹莫特治疗皮肤的慢性银屑病瘙痒。此外,我们观察到咪喹莫特诱导的自发抓挠行为在第21天消失。尽管如此，皮内注射PD-1/PD-L1抑制剂可以诱导更多的自发性抓挠超过一个月，表明咪喹莫特治疗的皮肤在自发抓挠行为消失后仍处于瘙痒致敏状态。在此期间,在咪喹莫特处理的小鼠皮肤和脊髓背角的PD-1受体表达显著增加，伴有脊髓背角小胶质细胞的显著激活。这些发现表明外周和中枢PD-1/PD-L1途径可能参与调节咪喹莫特诱导的慢性瘙痒和瘙痒致敏。
