cAMP levels in lymphocytes and CD4+ regulatory T-cell functions are affected by dopamine receptor gene polymorphisms
cAMP levels in lymphocytes and CD4+ regulatory T-cell functions are affected by dopamine receptor gene polymorphisms
复制标题
DOI：
10.1111/imm.12843
复制
发表时间：
2018-03-01
期刊：
影响因子：
6.4
通讯作者：
Marino, Franca
中科院分区：
文献类型：
--
作者：
Cosentino, Marco;Kustrimovic, Natasa;Marino, Franca
神经递质多巴胺（DA）在免疫系统中和免疫细胞之间具有显著的作用，CD 4（+）调节性T（Treg）淋巴细胞是一种对控制免疫稳态至关重要的特化T细胞亚群，对DA特别敏感。多巴胺能受体（DR）根据其药理学特征和主要的第二信使偶联分为两个家族：激活腺苷酸环化酶的D-1-样（D-1和D-5）和抑制腺苷酸环化酶的D-2-样（D-2、D-3和D-4），它们存在于与临床病症如精神分裂症、双相情感障碍、物质滥用和成瘾相关的几种变体中。我们的目的是检查，在静脉血样本从健康志愿者，之间的关系，任意DR评分和DR功能反应的人淋巴细胞。所有样本都进行了选定的DR基因变异（DRD 1：rs 4532和rs686; DRD 2：rs 1800497和rs6277; DRD 3：rs6280; DRD 4：rs747302和7个48碱基对可变数目串联重复序列（VNTR））的基因分型，并将DR评分归因于每位参与者。我们还测试了DR基因多态性是否可能影响Treg细胞抑制效应T细胞功能的能力。据我们所知，这是第一个研究表明DR基因变异和人类T淋巴细胞功能之间的相关性。主要结果是D-1样和D-2样DR在人淋巴细胞中具有功能活性，尽管与D-2样DR刺激相比，D-1样DR刺激导致更强的作用。此外，似乎DR基因谱可能影响淋巴细胞对多巴胺能药物的反应能力。需要更多的调查，这些发现可能的临床意义。
The neurotransmitter dopamine (DA) has prominent effects in the immune system and between the immune cells, CD4(+) regulatory T (Treg) lymphocytes, a specialized T-cell subset crucial for the control of immune homeostasis, are especially sensitive to DA. Dopaminergic receptors (DR) are grouped into two families according to their pharmacological profile and main second messenger coupling: the D-1-like (D-1 and D-5), which activate adenylate cyclase, and the D-2-like (D-2, D-3 and D-4), which inhibit adenylate cyclase and exist in several variants that have been associated to clinical conditions such as schizophrenia, bipolar disorder, substance abuse and addiction. We aimed to examine, in venous blood samples from healthy volunteers, the relationship between the arbitrary DR score and DR functional responses in human lymphocytes. All the samples were genotyped for selected DR gene variants (DRD1: rs4532 and rs686; DRD2: rs1800497 and rs6277; DRD3: rs6280; DRD4: rs747302 and seven 48-base pair variable number tandem repeat (VNTR)) and a DR score was attributed to each participant. We have also tested whether DR gene polymorphisms might affect Treg cell ability to suppress effector T-cell function. To our knowledge, this is the first study showing a correlation between DR gene variants and human T lymphocyte function. The main results are that both D-1-like and D-2-like DR are functionally active in human lymphocytes, although the D-1-like DR stimulation results in stronger effects in comparison to the D-2-like DR stimulation. In addition, it seems that the DR genetic profile may affect the ability of lymphocytes to respond to dopaminergic agents. More investigations are needed about the possible clinical relevance of such findings.