Extracellular vesicles derived from hADSCs rescue acute pancreatitis by carrying p-STK3 to regulate Treg differentiation

Severe acute pancreatitis (SAP) is a complex inflammatory disorder with severe immune imbalance. This study investigates the therapeutic potential of extracellular vesicles derived from human adipose mesenchymal stem cells (hADSC-EVs) in modulating Treg differentiation and alleviating SAP. We conducted a phosphoproteomics analysis to evaluate phosphorylation levels, and administered hADSC-EVs in a mouse model of SAP and assessed their impact on Treg differentiation. Phosphoproteomics revealed a significant increase in p-STK3 following hADSC-EVs treatment, restoring Foxp3 level diminished by STK3 knockdown. HADSC-EVs promoted Treg differentiation in a concentration-dependent manner by targeting Foxp3 transcription. In the SAP mouse model, hADSC-EVs improved survival rates and mitigated histopathological alterations. In conclusion, our study revealed that STK3 effectively promotes Treg differentiation and enhances their immunosuppressive capabilities, thereby ameliorating inflammation and attenuating the pathological phenotypes associated with SAP. These findings provide valuable insights into the potential role of hADSC-EVs in regulating immune responses and promoting tissue repair.