کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3063917 | 1580390 | 2015 | 12 صفحه PDF | دانلود رایگان |
• Adenylyl cyclase inhibition by dopamine receptor D3 favours CD4+ T-cell activation.
• Dopamine receptor D5 signalling increases ERK activity reinforcing T-cell activation.
• Late ERK2 inhibition exerted by dopamine receptor D3 enhances Th1-differentiation.
Dopamine receptors have been described in T-cells, however their signalling pathways coupled remain unknown. Since cAMP and ERKs play key roles regulating T-cell physiology, we aim to determine whether cAMP and ERK1/2-phosphorylation are modulated by dopamine receptor 3 (D3R) and D5R, and how this modulation affects CD4+ T-cell activation and differentiation. Our pharmacologic and genetic evidence shows that D3R-stimulation reduced cAMP levels and ERK2-phosphorylation, consequently increasing CD4+ T-cell activation and Th1-differentiation, respectively. Moreover, D5R expression reinforced TCR-triggered ERK1/2-phosphorylation and T-cell activation. In conclusion, these findings demonstrate how D3R and D5R modulate key signalling pathways affecting CD4+ T-cell activation and Th1-differentiation.
Journal: Journal of Neuroimmunology - Volume 284, 15 July 2015, Pages 18–29