Dopamine receptors modulate T lymphocytes via inhibition of cAMP-CREB signaling pathway.
OBJECTIVE
We have previously reported that dopamine D2-like receptors including D2, D3 and D4 receptors are more important in mediating modulation of T cells than dopamine D1-like receptors (D1 and D5 receptors). Here we aimed to clarify the role of D2-like receptors in regulation of differentiation and function of T lymphocyte subsets, including helper T (Th)1, Th2, Th17 and regulatory T (Treg) cells.


METHODS
Lymphocytes, separated from the mesenteric lymph nodes of mice, were stimulated with concanavalin A (Con A) and treated with the D2-like receptor agonist quinpirole or the antagonist haloperidol. Expression of lymphocyte cytokines and transcription factors and dopamine D2, D3 and D4 receptors were measured by real-time quantitative polymerase chain reaction and Western blot assay. Meanwhile, cAMP and phosphorylated cAMP-response element-binding (CREB) levels in the lymphocytes were examined by enzyme-linked immunosorbent assay and Western blot assay, respectively.


RESULTS
Activation of D2-like receptors with the agonist quinpirole upregulated the expression of Th2- and Treg-specific transcription factors and cytokines in Con A-activated lymphocytes, but downregulated the expression of Th1- and Th17-specific transcription factors and cytokines. Simultaneously, quinpirole increased dopamine D3 and D4 receptor expression, but did not alter D2 receptor expression. However, quinpirole reduced both cAMP and phosphorylated CREB levels in Con A-activated lymphocytes. All these quinpirole effects were blocked by haloperidol, an antagonist of D2-like receptors.


CONCLUSIONS
D2-like receptors, principally dopamine D3 and D4 receptors, promote differentiation and function of T lymphocytes towards anti-inflammatory T cell subsets by a negative link to cAMP-CREB pathway.
School of Biological and Basic Medical Sciences, Soochow University, Suzhou, China.
Yan
Y
Huang
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Can-Can
CC
Chen
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Ting-Ting
TT
Wang
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Yi-Hua
YH
Qiu
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Yu-Ping
YP
Peng
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D019257:Quinpirole / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D051786:Cyclic AMP Response Element Modulator; D019257:Quinpirole; D000242:Cyclic AMP