IMPDH2 promotes Psoriatic Inflammation through STAT3-Dependent Signaling in Keratinocytes

In this study, we employed an integrated approach combining bioinformatic analysis of multiple public transcriptomic datasets, experimental validation in psoriatic skin samples, and mechanistic investigations using both in vivo and in vitro models. By analyzing bulk RNA-sequencing (RNA-seq) and single-cell RNA-sequencing (scRNA-seq) datasets of psoriasis, we uncovered the IMPDH2 gene expression increased in keratinocytes of psoriasis patients, and also its increased protein level is further validated in psoriasis patients slides. We further investigated the therapeutic potential of targeting IMPDH2 using the inhibitor in a murine model of psoriasis-like dermatitis. Mechanistically, we demonstrate that IMPDH2 knockdown or inhibition impairs the phosphorylation of STAT3, thereby attenuating the IL-17 signaling pathway. Our findings reveal a novel link between nucleotide metabolism and inflammatory signaling, suggesting that IMPDH2 promotes psoriasis progression by facilitating the STAT3 siganaling in keratinocytes.