LB1642 Inhibition of spleen tyrosine kinase signaling pathway ameliorates imiquimod- induced psoriasis mouse model

Psoriasis is a chronic inflammatory skin disease with a strong genetic predisposition and autoimmune pathogenic traits. Psoriasis is found throughout the world, but the prevalence varies among different ethnic groups. The worldwide prevalence is about 2%. Psoriasis was originally thought of as a disorder primarily of epidermal keratinocytes. Spleen tyrosine kinase (SYK) signaling pathway was correlated with inflammatory responses and pathogenic T cell differentiation. However, it is still unknown whether inhibition of SYK activation would lead to down-regulation of psoriatic dermatitis. Therefore, the present study investigated the effect of the SYK inhibitor on imiquimod- induced psoriasis mouse model and IL-17A stimulated HaCaT cell. The results showed that R406, the SYK inhibitor, could inhibit the expression of IL-6 and IL-8 in IL-17A stimulated HaCaT cells at the dose without cytotoxicity. In in vivo results, R406 decreased symptoms of psoriasis, including ear thickness, skin redness, and scaling. The pathology showed that immune cells infiltration was significantly decreased in the R406 treatment group. The expression of Th17 cells in splenocytes was significantly suppressed by R406. In conclusion, R406 may be a promising therapeutic candidate for the treatment of psoriasis.