Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania (B.C., S.M.M., E.A.N-B., Y.A., J.W., P.J.G.); and The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania (V.P.).
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania (B.C., S.M.M., E.A.N-B., Y.A., J.W., P.J.G.); and The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania (V.P.)
Pharmacol Rev. 2023 Jan;75(1):62-158. doi: 10.1124/pharmrev.122.000618. Epub 2022 Dec 8.
The neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions in peripheral organs, such as blood pressure, renal activity, and intestinal motility. Beyond these functions, a growing body of evidence indicates that dopamine is an important immunoregulatory factor. Most types of immune cells express dopamine receptors and other dopaminergic proteins, and many immune cells take up, produce, store, and/or release dopamine, suggesting that dopaminergic immunomodulation is important for immune function. Targeting these pathways could be a promising avenue for the treatment of inflammation and disease, but despite increasing research in this area, data on the specific effects of dopamine on many immune cells and disease processes remain inconsistent and poorly understood. Therefore, this review integrates the current knowledge of the role of dopamine in immune cell function and inflammatory signaling across systems. We also discuss the current understanding of dopaminergic regulation of immune signaling in the CNS and peripheral tissues, highlighting the role of dopaminergic immunomodulation in diseases such as Parkinson's disease, several neuropsychiatric conditions, neurologic human immunodeficiency virus, inflammatory bowel disease, rheumatoid arthritis, and others. Careful consideration is given to the influence of experimental design on results, and we note a number of areas in need of further research. Overall, this review integrates our knowledge of dopaminergic immunology at the cellular, tissue, and disease level and prompts the development of therapeutics and strategies targeted toward ameliorating disease through dopaminergic regulation of immunity. SIGNIFICANCE STATEMENT: Canonically, dopamine is recognized as a neurotransmitter involved in the regulation of movement, cognition, and reward. However, dopamine also acts as an immune modulator in the central nervous system and periphery. This review comprehensively assesses the current knowledge of dopaminergic immunomodulation and the role of dopamine in disease pathogenesis at the cellular and tissue level. This will provide broad access to this information across fields, identify areas in need of further investigation, and drive the development of dopaminergic therapeutic strategies.
神经递质多巴胺是中枢神经系统 (CNS) 功能的关键因素，调节包括奖励、运动和认知在内的许多过程。多巴胺还调节外周器官的关键功能，如血压、肾脏活动和肠道蠕动。除了这些功能，越来越多的证据表明多巴胺是一种重要的免疫调节因子。大多数类型的免疫细胞表达多巴胺受体和其他多巴胺能蛋白，许多免疫细胞摄取、产生、储存和/或释放多巴胺，这表明多巴胺能免疫调节对免疫功能很重要。针对这些途径可能是治疗炎症和疾病的有前途的途径，但尽管在这一领域的研究不断增加，关于多巴胺对许多免疫细胞和疾病过程的具体影响的数据仍然不一致且理解不足。因此，本综述整合了目前关于多巴胺在免疫细胞功能和炎症信号转导中的作用的知识。我们还讨论了多巴胺对中枢神经系统和外周组织中免疫信号的调节作用的现有认识，强调了多巴胺能免疫调节在帕金森病、几种神经精神疾病、神经人类免疫缺陷病毒、炎症性肠病、类风湿关节炎等疾病中的作用。我们仔细考虑了实验设计对结果的影响，并注意到需要进一步研究的几个领域。总的来说，本综述整合了我们在细胞、组织和疾病水平上对多巴胺免疫生物学的认识，并促使通过多巴胺调节免疫来开发治疗疾病的疗法和策略。
通常，多巴胺被认为是一种参与调节运动、认知和奖励的神经递质。然而，多巴胺在中枢神经系统和外周组织中也作为一种免疫调节剂发挥作用。本综述全面评估了目前关于多巴胺免疫调节作用的知识以及多巴胺在细胞和组织水平上疾病发病机制中的作用。这将为跨领域广泛获取这些信息提供便利，确定需要进一步研究的领域，并推动多巴胺治疗策略的发展。
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