Context: It has been demonstrated that dopamine (DA) plays an important role in numerous cellular processes of T cell. Accumulating evidence suggests that the outcomes of T cell treatment with DA is depended on DA concentrations, T cell subtypes and activation states. However, the detail mechanism of DA function on T cell activation or regulatory T cells is largely unclear.
Objective: This study aims to explore the mechanisms by which DA regulates the activation of CD4+ T cells and the function of Tregs.
Materials and methods: T cell proliferation was detected using CCK-8, BrdU incorporation assay or eFluor 450 cell labeling assay, and Western blot were used to detect phosphorylation of p65 and Erk. Nuclear translocation of transcription factors including p65, FOXO1 and NFAT1 were observed under laser confocal microscopy.
Results: Our present study demonstrated that DA (17 µM) can directly promote CD4+ T cells activation through D2-like receptors by enhancing the phosphorylation of p65, also can impair regulatory CD4+ T cells (Tregs) stability and suppressive function through D1- and D2-like receptors by inhibiting the expression of FOXO1 and NFAT1, which are the transcriptional factors of FOXP3, and by suppressing the expression of IL-10 in Tregs. Injection of DA can inhibit tumor growth in vivo.
Conclusions: These data indicate a critical role for DA in promotion of CD4+ T helper response, this may applicable in tumor treatment in the future.
Keywords: CD4+ T cells; FOXO1; FOXP3; NFAT1; Tregs; dopamine.