Tm4sf19 inhibition alleviates imiquimod-induced psoriatic dermatitis by regulating inflammatory signaling pathways and keratinocyte proliferation in mice.

Abstract

BACKGROUND: Psoriasis is a chronic inflammatory disease characterized by keratinocyte hyperproliferation, immune cell infiltration, and persistent inflammatory signaling. Although Tm4sf19 has been implicated in inflammatory processes, its contribution to psoriasis pathogenesis remains unclear. METHODS: We investigate the role of Tm4sf19 in psoriatic inflammation was examined using an imiquimod-induced psoriasis mouse model and HaCaT keratinocytes, in which Tm4sf19 expression was deleted genetically or suppressed pharmacologically with the competitive inhibitor, LEL-Fc. Gene expression, protein expression, and tissue changes were assessed by qPCR, western blotting and histological scoring, respectively. RESULTS: Tm4sf19 expression was significantly elevated in psoriatic lesion. Tm4sf19 knockout or inhibition using LEL-Fc suppressed psoriatic symptoms, macrophage-mediated inflammation and inflammatory cytokine expression. Tm4sf19 inhibition also suppressed the activation of STAT3, EGFR, ERK and KRT17 signaling pathways in keratinocytes. Furthermore, LEL-Fc treatment effectively inhibited LPS-induced cell cycle progression and promoted apoptosis in keratinocyte both in vivo and in vitro. CONCLUSION: These findings suggest that Tm4sf19 regulates psoriatic inflammation and keratinocyte proliferation through major signaling pathways. Therefore, inhibiting Tm4sf19 may have therapeutic potential for the treatment of psoriasis.