Schistosoma Japonicum Heat Shock Protein 60 Enhances Regulatory T Cell Immunosuppressive Function By Promoting The Expressions Of IL-10 And TGF-β

Objective To explore the effect of Schistosoma japonicum heat shock protein 60(Sj HSP60)on CD4~+CD25~+regulatory T cell(Treg)immunosuppressive function and its possible mechanisms.Methods Ex vivo and in vitro methods were used to investigate the effect of Sj HSP60 on Treg immunosuppressive activity.Intracellular cytokine staining combined with flow cytometry and ELISA were used to detect the expression levels of IL-10 and TGF-βby Tregs stimulated with Sj HSP60.Co-cultures in transwells and in vitro suppression assay were performed to investigate how Sj HSP60 enhanced the immunosuppressive function of Tregs.And flow cytometry was also used to analyze the expressions of Foxp3 and CTLA-4 in Tregs.Finally,histological examinations(hematoxylin-eosin and Sirius red staining)and serum enzymology testing were performed to investigate the protective effect of Sj HSP60 against hepatic pathological damage in schistosome-infected mice.Results Sj HSP60 enhanced the immunosuppressive function of Tregs.Soluble cytokines IL-10 and TGF-βmediated inhibitory activity of Sj HSP60-triggered Tregs.Sj HSP60induced significant increases in both IL-10 and TGF-βexpressions of Tregs.Further investigation showed significant increased Foxp3 and CTLA-4 in Sj HSP60-triggered Tregs.In addition,the hepatic granulomatous responses and severity of liver fibrosis and injury in schistosome-infected mice treated with Sj HSP60 were significantly reduced.Conclustion Sj HSP60 enhances Treg immunosuppressive function by promoting the expression of IL-10 and TGF-β,possibly due to Sj HSP60-induced Foxp3 and CTLA-4 in Tregs.In addition,Sj HSP60 contributes to the restriction of hepatic immunopathology in mice with schistosome infection.