Study On The Change And Role Of Monocytic Myeloid-derived Suppressor Cells In Acute Pancreatitis

BACKGROUND&AIMS:Severe acute pancreatitis(SAP)patients have high mortality due to enhanced systemic inflammation and multiple organ failure in the early stage.Immunocytes play an important immunoregulatory role in the development of systemic inflammation in AP.Myeloid-derived suppressor cells(MDSCs)produce immunosuppressive effects in the pathogenesis of inflammation and infection by inhibiting T cells.In experimental models of SAP,monocytic MDSCs(M-MDSCs)are significantly activated,but their role in AP remains unclear.This study was aiming to observe the change and role of M-MDSCs in the early stage of AP,to elucidate the mechanism,and to provide new ideas for the early diagnosis and treatment of SAP.METHODS:Cloud database was established to record clinical data of AP patients and their plasma was collected and frozen.ASB600 protein chip and AAH-BLG-507 protein chip were used to detect and analyze the differential expression of plasma proteins in 4 health controls,6 patients with hyperlipidemic AP and 6 patients with biliary AP.The expression of S100A8and S100A9 of more hyperlipidemic AP patients was detected by ELISA.M-MDSCs,T cell subtypes and HLA-DR expression of M-MDSCs were detected by flow cytometry.Luminex assay was used to detect myeloid related cytokines/chemokines and their correlations with M-MDSCs were analyzed.The ROC curve was used to study the early predictive effect of M-MDSCs and HLA-DR expression on SAP.We also establish AP model in Lys M^creSTAT3^f/f mice to study the influence of STAT3 gene knockout on M-MDSCs and their HLA-DR expression.RESULTS:Clinical data of AP patients collected in Cloud database can be used for clinical and experimental research.Protein microarray analysis showed that there were many differentially expressed proteins in AP patients with different severity.Go-slim analysis showed that these proteins were highly enriched in the immune response and the up-regulation of S100A8was the most obvious.ELISA showed that the expressions of S100A8 and S100A9 in SAP and MSAP patients were significantly increased.M-MDSCs and related cytokines/chemokines increased significantly in early stage of SAP,which were related to decreased HLA-DR expression and impaired T cell response.The area under the ROC curve analysis showed M-MDSCs and their HLA-DR expression can be used as early predictors of AP severity.Lastly,the expansion and activation of M-MDSCs were associated with the STAT3 pathway in experimental AP model.CONCLUSION:M-MDSCs increased significantly in the early stage of AP and was related to the severity of AP.M-MDSCs were amplified and activated through STAT3 pathway and involved in systemic inflammatory response in AP mice.Therefore,immunotherapy targeting M-MDSCs may become a new direction of SAP therapy.