FOXE1 promotes the progression of pulp inflammation by activating PANoptosis in dental pulp cells.

PANoptosis is a type of programmed cell death (PCD) that is characterized by the simultaneous activation of pyroptosis, necroptosis, and apoptosis. This process triggers amplified inflammatory responses, which may compromise the success of vital pulp therapy (VPT). In this study, a PANoptotic dental pulp cell (DPC) cluster was identified in single-cell RNA sequencing data from inflamed dental pulp tissue. The occurrence of PANoptosis was further confirmed in human clinical pulpitis samples, primary cultured DPCs, and a mouse experimental pulpitis model. We subsequently identified forkhead box E1 (FOXE1) as a key transcription factor that regulates PANoptosis in DPCs. Moreover, FOXE1 knockdown in DPCs and mouse dental pulp tissue effectively suppressed PANoptosis and attenuated inflammatory responses. Our study demonstrated that PANoptosis plays an important role in pulpitis and that FOXE1 may represent a promising therapeutic target for VPT by regulating the progression of pulp inflammation.