MAPK pathway inhibitors alleviate T lymphocyte immune suppression by regulating PD-L1 expression in bacterial sepsis / 免疫学杂志

ABSTRACT

This study was performed to investigate the effects of mitogen-activated protein kinase(MAPK)pathway inhibitors on the expression of PD-L1 in dendritic cells and the T lymphocyte immune response in gram negative bacterial sepsis.The immunosuppression model of bacterial sepsis was established by treating the dendritic cells with bacterial endotoxin.The MAPK pathways inhibitors were applied to block pathways of dendritic cells,and then the PD-L1 expression on dendritic cells were detected by flow cytometry and Western blotting.Furthermore,the levels of T lymphocyte proliferation response and cytotoxic T cell response in mixed lymphocyte co-culture experiments were detected by cell proliferation assay kit and enzyme-linked immunospot assay kit,respectively.Data showed that the PD-L1 expression of dendritic cells were significantly up-regulated in the model group compared with the control group,while the levels of T lymphocyte proliferation response and cytotoxic T cell response in the model group were significantly reduced(P<0.05).Then compared with the model group,the PD-L1 expression of dendritic cells were significantly down-regulated in the SB203580/model group(P<0.05),meanwhile the levels of T lymphocyte proliferation response and cytotoxic T cell response were both significantly increased in SB203580/model group and αPD-L1/model group(P<0.05).In conclusion,the p38 signaling pathway could regulate PD-L1 expression of dendritic cells in bacterial sepsis.The application of p38 pathway inhibitors could partially reduce the PD-L1 expression of dendritic cells and reverse T lymphocyte immunosuppression in bacterial sepsis.