CRISPR/Cas9-Mediated Knockout and Overexpression Studies Unveil the Role of PD-L1 in Immune Modulation in a Psoriasis-like Mouse Model

• DOI: 10.1007/s10753-025-02281-w
• Publication Date: 2025-04-04T18:42:31Z
• Authors: Chunjie Gao; Yunxi Cai; Xinxin Wu; Jiankun Song; Qi Zheng; Mingxia Wang; Ying Luo; Yue Luo; Xiaoya Fei; Ying Zhang; Yang Yang; Le Kuai; Yi Ru; Seokgyeong Hong; Na Tian; Bin Li; Zhan Zhang
• Keywords: Knockout mouse; Immune checkpoint

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 responses, particularly inhibiting immature Th cells into Th17 cells. This study aims examine the effect PD-L1 psoriasis progress, which is condition characterized by response dominated We constructed knockout (PD-L1KO) and overexpression (PD-L1OE) mice through CRISPR/Cas9 technology assess impact imiquimod (IMQ)-induced psoriasis-like mouse model. In comparison IMQ, ear thickness exhibited a reduction, PASI score decreased, HE sections revealed thinning epidermal spines PD-L1OE mice. PD-L1KO mice, however, showed opposite results. Moreover, immunohistochemical assessments skin lesion tissues demonstrated heightened proliferation inflammatory infiltration group, accompanied elevated tissue expression proliferating cell nuclear antigen (PCNA), Nuclear factor kappa-light-chain-enhancer activated B (NF-κB) p50, F4/80 IMQ-treated WT absence IMQ-induced was found intensify response, as evidenced phosphorylated signal transducers activators transcription 3 (pSTAT3) CD3 affected compared both According our findings, plays important roles inflammation, proliferation, regulating responses. Targeting may present promising therapeutic strategy for management psoriasis.