Regulatory B cells attenuate sepsis-associated pancreatic injury by regulating T cell homeostasis

Sepsis is a common and life-threatening syndrome resulting from systemic and dysregulated immune response to severe infection, which contributes to morbidity and mortality in critically ill patients. This work aimed to evaluate the regulatory function of Breg cells in sepsis-associated pancreatic injury. We established mice model of sepsis-associated pancreatic injury by cecal ligation and puncture (CLP). Pancreatic injury was assessed by measuring the levels of amylase activity and histologic pancreatic injury scores. The proportions of Breg cells and T cell subsets were analyzed by flow cytometry, their secreted cytokines were detected by ELISA. The expressions of T-bet, RORγt and Foxp3 in spleen were determined by RT-PCR. The apoptosis of pancreatic cells was examined by LDH assay and Tunel, and the cell viability was detected by MTT assay. Compared to the sham group, a significantly lower percentage of Breg cells was observed in model mice. Anti-CD22 treatment exacerbated pancreatic injury, and significantly increased the percentages of Th1, Th17 cells along with the levels of IFN-γ, IL-17 in CLP-induced sepsis model, but did not affect the differentiation of Treg cells and expression of IL-10. Anti-CD22 administration promoted the expressions of T-bet and RORγt, but did not affect the Foxp3 expression. Adoptive transfer Breg cells remarkably alleviated pancreatic injury, and significantly decreased the percentages of Th1, Th17 cells along with the levels of IFN-γ, IL-17 and further promoted the percentage of Treg cells and expression of IL-10 in CLP-induced sepsis model. Moreover, adoptive transfer Breg cells inhibited the expressions of T-bet and RORγt, and promoted Foxp3 expression in model mice. Lipopolysaccharide (LPS) promoted the apoptosis in pancreatic acinar cells, which was inhibited after culturing with Breg cells in vitro. LPS remarkably upregulated the differentiation of Th1 and Th17 cells, and downregulated the differentiation of Treg cells, which could be significantly reversed by Breg cells in vitro. In conclusion, Breg cells may exhibit the protective effects by modulating T cell responses along with the cytokines in sepsis-associated pancreatic injury.