The Tim-3/galectin-9 axis interferes with Th1/Th2 cell balance and induces lymphocyte apoptosis in patients with sepsis

Sepsis is characterized by T cell immune imbalance, particularly between Th1 and Th2 cells, and is mediated by pro- and anti-inflammatory cytokines. However, the mechanism underlying the immune regulation of sepsis remains poorly understood. Here, the mechanism of Th1/Th2 balance in patients with sepsis was investigated. Peripheral blood was collected from patients with sepsis and healthy controls and the proportion of CD3(+)CD4(+) T cells was analyzed by flow cytometry. Soluble (s) Tim-3, galectin-9 (Gal-9), IFN-gamma and IL-4 were determined by ELISA, and the mRNA expression of Tim-3, Gal-9, T-bet and GATA-3 were analyzed via RT-qPCR. Following Tim-3 silencing in lymphocytes using anti-Tim-3 antibodies, the content of IFN-gamma and IL-4 was detected by ELISA. In addition, the apoptosis rate of lymphocytes was evaluated by PI/Annexin V staining, and the associations between Tim-3, Gal-9, IFN-gamma and IL-4 were analyzed by Pearson's correlation coefficient. Data indicated that Tim-3(+) T cells were increased. Additionally, the levels of soluble Tim-3, Gal-9, IL-4 and GATA-3 were increased, while those of IFN-gamma and T-bet were decreased. When the expression of Tim-3 was inhibited, the levels of IFN-gamma were upregulated and the apoptosis rate of lymphocytes was reduced. However, no significant changes were observed in the expression of IL-4. Furthermore, a positive association between Tim-3 and Ga-9, and a negative association between Tim-3 and IFN-gamma was identified. The current study suggested that Tim-3 combined with Gal-9 could regulate the balance of Th1/Th2 cells and induce lymphocyte apoptosis in patients with sepsis.