Resveratrol Ameliorates Immunosuppression of T Lymphocytes in Septic Rats by Inhibiting PD-L1 Expression on Neutrophils

Abstract

Background & Aims: Resveratrol (RES), as a natural compound, has demonstrated potential therapeutic effects in sepsis and anti-immune suppression properties in various diseases. However, during the development of sepsis, immune suppression is primarily caused by T-cell dysfunction. Therefore, this study aims to explore the specific mechanisms by which RES regulates the immunosuppression of T lymphocytes in septic rats. Method: Initially, we simulated the pathological state of sepsis in rats using the cecal ligation and puncture (CLP) model and treated them with RES. The therapeutic effect of RES was assessed by observing the survival rate of CLP rats. Subsequently, we determined the protein expression levels of programmed death-ligand 1 (PD-L1) and Programmed death-1 (PD-1) in blood, as well as the number of PD-L1-positive neutrophils. We also assessed the histopathological morphology and apoptosis in the spleen and thymus, along with the levels of inflammatory factors. Finally, neutrophils were isolated from both the Sham and CLP groups, co-cultured with T lymphocytes, and the apoptosis rate of T lymphocytes was examined. Results: We observed that RES boosted the survival rate of CLP rats. Additionally, RES inhibited the expression of PD-L1 on neutrophils and exhibited a mitigating effect on immunosuppression of T lymphocytes. This was demonstrated by the improvement in the histopathological structure of the spleen and thymus in CLP rats, along with the inhibition of apoptosis in T lymphocyte by RES. Conclusion: RES alleviates immunosuppression of T lymphocytes in septic rats by inhibiting PD-L1 expression on neutrophils. Consequently, RES enhances the survival rate of CLP rats.