<p>The role of programmed death-ligand 1 (PD-L1), an essential immune checkpoint protein, has garnered considerable interest in recent years due to its influence on immune responses, particularly inhibiting immature Th cells into Th17 cells. This study aims to examine the effect of PD-L1 on psoriasis progress, which is the condition characterized by an immune response dominated by Th17 cells. We constructed the PD-L1 knockout (PD-L1^KO) and overexpression (PD-L1^OE) mice through CRISPR/Cas9 technology to assess the impact of PD-L1 in an imiquimod (IMQ)-induced psoriasis-like mouse model. In comparison to IMQ, the ear thickness exhibited a reduction, the PASI score decreased, and HE sections revealed a thinning of the epidermal spines in PD-L1^OE mice. PD-L1^KO mice, however, showed opposite results. Moreover, immunohistochemical assessments of the skin lesion tissues demonstrated heightened epidermal proliferation and inflammatory infiltration in the PD-L1^KO group, accompanied by elevated tissue expression of proliferating cell nuclear antigen (PCNA), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50, and F4/80 in comparison to IMQ-treated and WT mice. The absence of PD-L1 in IMQ-induced mice was found to intensify the immune response, as evidenced by heightened expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT3) and CD3 in the affected tissues compared to both IMQ-treated and WT mice. According to our findings, PD-L1 plays important roles in inhibiting inflammation, proliferation, and regulating immune responses. Targeting PD-L1 may present a promising therapeutic strategy for the management of psoriasis.</p>