The function and mechanism of dopamine in the activation of CD4⁺ T cell

Abstract

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
• Tregs
• dopamine
• FOXO1
• NFAT1
• FOXP3

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

All data included in this study are available upon request by contact with the corresponding authors.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 81771667, 31800736, 81771676, 81970027, 81870025, 81770115, 82070009, 82071765), Natural Science Foundation of Jiangsu Province to Yi Yang (grant number: BK20170349), Social Development Project of Jiangsu Province (grant number: BE2016676, BE2019671), Program for Changjiang Scholars and Innovative Research Team in University (grant numbers: PCSIRT, IRT1075) and Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences of Soochow University. Key Lab of Respiratory Disease of Suzhou (grant number: SZS201714), and Translational Research Grant of NCRCH (grant number: 2020ZKZC04).