IL-17A and TNF-α-induced Dectin-1 expression may promote keratinocyte proliferation in psoriatic lesions

Background: 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-alpha. 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-alpha 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. Objectives: To elucidate how IL-17A and TNF-alpha may promote keratinocyte proliferation in psoriatic lesions and whether Dectin-1 is involved. Materials & Methods: 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-alpha in psoriatic lesions. Finally, we investigated the signalling pathway through which Dectin-1 may promote keratinocyte proliferation. Results: Dectin-1 was significantly increased in keratinocytes from psoriatic lesions. Moreover, IL-17A and TNF-alpha effectively induced the expression of Dectin-1 in HaCaT cells, which was shown to activate the Syk/NF-kappa B signalling pathway and promote the proliferation of keratinocytes. Conclusion: IL-17A and TNF-alpha 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.