Serpine1 plays a critical role in Th17 cell differentiation and psoriasis pathogenesis

A large body of evidence indicates that Th17 cells play essential roles in mucosal immune responses and trigger autoimmune diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. Targeting Th17 cells holds promise for therapeutic innovation. However, the molecular mechanisms underlying Th17 cell differentiation remain poorly understood. Here, we found that Serpine1 was preferentially induced in Th17 cells. Genetic ablation of Serpine1 inhibited Th17 cell polarizationin vitro, reproducing the phenotype caused by pharmaceutical inhibition against Serpine1 product PAI-1. Moreover, we confirmed that, despite normal T-cell initiationin vivo, deletion or inhibition of Serpine1 significantly attenuated disease severity and notably reduced skin inflammation in an IMQ-induced psoriasis model. Notably, this protective effect was also recapitulated in the CD4 conditional knockout mouse pathogenic model, ruling out the non-T cell autologous effect of Serpine1. Collectively, our results revealed a critical role of Serpine1 in regulating Th17 cell differentiation and autoimmune diseases, suggesting that Serpine1 is a promising therapeutic target for autoimmune disease treatment.