T cells and their immunometabolism: a novel way to understanding sepsis immunopathogenesis and future therapeutics

Sepsis has always been considered as a big challenge for pharmaceutical companies in terms of discovering and designing new therapeutics. The pathogenesis of sepsis involves aberrant activation of innate immune cells (i.e. macrophages, neutrophils etc.) at early stages. However, a stage of immunosuppression is also observed during sepsis even in the patients who have recovered from it. This stage of immunosuppression is observed due to the loss of conventional (i.e. CD4, CD8) T cells, Th17 cells and an upregulation of regulatory T cells (Tregs). This process also impacts metabolic processes controlling immune cell metabolism called immunometabolism. The present review is focused on the T cell-mediated immune response, their immunometabolism and targeting T cell immunometabolism during sepsis as future therapeutic approach. The first part of the manuscripts describes an impact of sepsis on conventional T cells, Th17 cells and Tregs along with their impact on sepsis. The subsequent section further describes the immunometabolism of these cells (CD4, CD8, Th17, and Tregs) under normal conditions and during sepsis-induced immunosuppression. The article ends with the therapeutic targeting of T cell immunometabolism (both conventional T cells and Tregs) during sepsis as a future immunomodulatory approach for its management

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.</jats:p