Abstract：
Psoriasis is a common skin disease with a high recurrence rate. Aberrant keratinocyte proliferation is a significant pathogenic characteristic of psoriatic lesions, and studies have revealed that the development of psoriasis is significantly influenced by pro-inflammatory cytokines, such as IL-17A and TNF-α. Biologics targeting these cytokines have been widely used in psoriasis treatment and achieve remarkable effects, however, the underlying mechanism of how IL-17A and TNF-α specifically regulate keratinocyte proliferation has not been fully elucidated. Dectin-1 is an essential membrane protein that is directly related to the immune microenvironment and the proliferation of multiple cell types. To elucidate how IL-17A and TNF-α may promote keratinocyte proliferation in psoriatic lesions and whether Dectin-1 is involved. The expression of Dectin-1 in keratinocytes from psoriatic lesions was detected by real-time PCR, western blot and immunofluorescence. Correlation analysis and cytological experiments were then performed to determine the relationship between Dectin-1 and IL-17A/TNF-α in psoriatic lesions. Finally, we investigated the signalling pathway through which Dectin-1 may promote keratinocyte proliferation. Dectin-1 was significantly increased in keratinocytes from psoriatic lesions. Moreover, IL-17A and TNF-α effectively induced the expression of Dectin-1 in HaCaT cells, which was shown to activate the Syk/NF-κB signalling pathway and promote the proliferation of keratinocytes. IL-17A and TNF-α may promote the proliferation of keratinocytes in psoriatic lesions through induction of Dectin-1, indicating that Dectin-1 could be a potential therapeutic target for the treatment of psoriasis.
摘要：
银屑病是一种常见的皮肤病，复发率高。异常的角质形成细胞增殖是银屑病病变的重要致病特征，研究表明，银屑病的发展受到促炎细胞因子的显著影响，例如IL-17A和TNF-α。以这些细胞因子为靶点的生物制剂已广泛应用于银屑病的治疗中,然而,IL-17A和TNF-α特异性调节角质形成细胞增殖的潜在机制尚未完全阐明。Dectin-1是一种必需的膜蛋白，与免疫微环境和多种细胞类型的增殖直接相关。阐明IL-17A和TNF-α如何促进银屑病皮损中的角质形成细胞增殖以及Dectin-1是否参与其中。实时荧光定量PCR检测Dectin-1在银屑病皮损角质形成细胞中的表达,免疫印迹和免疫荧光。然后进行相关分析和细胞学实验，以确定银屑病皮损中Dectin-1和IL-17A/TNF-α的关系。最后,我们研究了Dectin-1促进角质形成细胞增殖的信号通路。银屑病病变的角质形成细胞中的Dectin-1显着增加。此外，IL-17A和TNF-α有效诱导HaCaT细胞Dectin-1表达,显示激活Syk/NF-κB信号通路并促进角质形成细胞的增殖。IL-17A和TNF-α可能通过诱导Dectin-1促进银屑病皮损角质形成细胞的增殖，表明Dectin-1可能是治疗银屑病的潜在治疗靶点。
