Tim-3/galectin-9 regulates Th1/Th2 cell balance in lipopolysaccharide-induced human lymphocytes

Abstract

Objective To investigate the mechanism of Tim-3/galectin-9 in T helper type 1/2 (Th1/Th2) cell imbalance in lipopolysaccharide(LPS)-induced human lymphocytes. Methods Peripheral blood mononuclear cells (PBMC) were isolated from patients with sepsis. The expression of Tim-3, galectin-9, T-bet and GATA3 were detected by RT-qPCR; ELISA was used for detecting sTim-3, galectin-9, IFN-γ and IL-4.Isolated peripheral blood mononuclear cells were incubated with LPS and then cytokines related to Th1 and Th2 cells in the supernatant of cell culture were detected by ELISA; Western blot was used to detect the expression of JAK2/STAT3 related factors; Pearson correlation coefficient analysis was performed to identify relationship among Tim-3, galectin-9,IFN-γ and IL-4. Results The mRNA expression of Tim-3 and galectin-9 in peripheral blood of patients with sepsis was increased, and protein expression of Tim-3, galectin-9, IL-4 and GATA-3 was increased significantly. The levels of IFN-γ and T-bet were decreased and levels of p-JAK2 and p-STAT3 were elevated. After blocking Tim-3 expression, IFN-γ level increased, while IL-4 level decreased significantly. Phosphorylation of JAK2 and STAT3 decreased. Level of Tim-3 and of IL-4 was positively correlated with galectin-9, while Tim-3 was negatively correlated with IFN-γ;IFN-γ was negatively correlated with galectin-9, and Tim-3 was positively correlated with IL-4. Conclusions Tim-3/galectin-9 regulates the JAK2/STAT3 pathway and leads to the imbalance of Th1/Th2 cells in LPS induced inflammation.

Keywords

• tim-3|galectin-9|t helper cells|jak2/stat3 pathway|sepsis