Dexmedetomidine Directs T Helper Cells toward Th1 Cell Differentiation via the STAT1‐T‐Bet Pathway

Abstract

Dexmedetomidine is an α2 adrenergic receptor agonist that has been reported to modulate the polarization of CD4+ T cells. However, the underlying mechanisms by which dexmedetomidine induces T-helper 1 (Th1) cell differentiation remain poorly understood. The aim of this study was to explore the potential mechanisms through which dexmedetomidine can induce Th1 cell differentiation. Purified CD4+ T cells were stimulated with anti-CD3/anti-CD28 and then treated with dexmedetomidine. Flow cytometry analysis was adopted to measure the concentration of Th1 cells. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR) were performed to detect protein levels and mRNA expression, respectively, of IFN-γ and IL-4. Western blotting was used to determine the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and T-bet expression. The Th1 cell subset and IFN-γ levels were elevated in the dexmedetomidine-induced CD4+ T cells. Dexmedetomidine enhanced the phosphorylation of STAT1 and the expression of T-bet in the CD4+ T cells. Atipamezole (an α2 adrenergic antagonist) and fludarabine (a STAT1 inhibitor) reversed the dexmedetomidine-induced Th1 cell differentiation. These results suggested that dexmedetomidine induced Th1 cell differentiation via the STAT1-T-bet signaling pathway.

Effects of Jianpi Huayu Decoction on Th1/Th2 Immune Balance in Mice With Liver Cancer-Related Fatigue via the IL- 27/STAT1 Signaling Pathway

“…Studies have shown that STAT1 can cause CD4+ T cells to differentiate into Th1, and its signaling pathway blocks GATA-3 transcription, thus suppressing Th2 differentiation and controlling Th1/Th2 balance. 36 , 37 IL-27, a member of the IL-12 family, has a significant part in the immune response and can directly trigger apoptosis in tumor cells by engaging with various immune cells in the body, such as CD4+ T cells, CD8+ T cells, regulatory T cells, natural killer cells, and dendritic cells. Moreover, IL-27 stimulates immune cells to release particular cytokines, thus controlling both cellular and humoral immunity and indirectly restraining tumor growth.…”

Post-translational modifications and immune responses in liver cancer

“…These phosphorylation events play a critical role in dictating T cell fates and functions. The phosphorylation of specific transcription factors, such as signal transducer and activator of transcription 1 (STAT1) in Th1 cells, STAT6 in Th2 cells, and STAT3 in Th17 cells, contributes to their differentiation and functional specialization (17)(18)(19)(20)(21). In patients with HCC, Th1 cytokines of serum level are often suppressed, while Th2 cytokines are frequently elevated (22).…”