Dopamine in the Immune System: Dopamine Receptors in Immune Cells, Potent Effects, Endogenous Production and Involvement in Immune and Neuropsychiatric Diseases

Levite, Mia

doi:10.1007/978-3-7091-0888-8_1

Cited by 24 publications

(34 citation statements)

References 98 publications

(201 reference statements)

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“…The functions of dendritic cells (DC) are sensitive to dopaminergic regulation (Levite, 2012; De Kleer et al, 2014; Prado et al, 2012; Chen et al, 2012). Functions of antigen-presenting DC change with differentiation and maturation.…”

Section: Dopamine Regulation Of the Peripheral Immune Systemmentioning

confidence: 99%

“…These findings are consistent with the proposed role of DCs as mediators of the innate immune system both within and between the innate and adaptive immune systems. In both cases, DC functions have been shown to be sensitive to dopaminergic regulation (Levite, 2012; De Kleer et al, 2014). Specifically, D5R activation, but not D2R inhibition, modulates DC stimulation and increases production of IL-12 and IL-23 (Prado et al, 2012; Chen et al, 2012).…”

Section: Dopamine Regulation Of the Peripheral Immune Systemmentioning

confidence: 99%

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The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

Mackie

Lebowitz

Saadatpour

et al. 2018

Brain, Behavior, and Immunity

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The second-most common neurodegenerative disease, Parkinson's Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission. The dopamine transporter (DAT), the main regulator of dopaminergic tone in the CNS, is known to exist in lymphocytes and monocytes/macrophages, but little is known about peripheral DAT biology or how DAT regulates the dopaminergic tone, much less how peripheral DAT alters immune function. Our review is guided by the hypothesis that dysfunctional peripheral dopamine signaling might be linked to the dysfunctional immune responses in PD and thereby suggests a potential bidirectional communication between central and peripheral dopamine systems. This review seeks to foster new perspectives concerning PD pathogenesis and progression.

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Section: Dopamine Regulation Of the Peripheral Immune Systemmentioning

confidence: 99%

Section: Dopamine Regulation Of the Peripheral Immune Systemmentioning

confidence: 99%

The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

Mackie

Lebowitz

Saadatpour

et al. 2018

Brain, Behavior, and Immunity

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“…During the past two decades, several studies have shown the capability of several neurotransmitters to regulate the function and differentiation of immune cells, including acetyl-choline, serotonin, glutamate, and dopamine (DA) among others (11)(12)(13)(14)(15)(16)(17)(18). Regarding expression of DA receptors (DARs) in immune cells, these receptors have been found not only in cells of the innate immune response such as dendritic cells (DCs), NK cells, macrophages/monocytes and granulocytes (19)(20)(21) but also in cells of the adaptive immune response such as B cells, CD8 + T cells, and CD4 + T cells (22)(23)(24)(25)(26)(27)(28)(29)(30).…”

Section: P Arkinson's Disease (Pd) Is a Neurodegenerative Disordermentioning

confidence: 99%

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

González

Contreras

Prado

et al. 2013

The Journal of Immunology

131

145

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Emerging evidence has demonstrated that CD4+ T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4+ T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4+ T cells. In this study, we examined the role of D3R expressed on CD4+ T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4+ T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4+ T cells but not when transferred with D3R-deficient CD4+ T cells. In agreement, experiments analyzing activation and differentiation of CD4+ T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4+ T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

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“…DA is however also increasingly regarded as a crucial transmitter in the neuroimmune network, contributing to the CNS-immune system interplay as well as in the communication among immune cells (Basu and Dasgupta 2000;Sarkar et al 2010;Levite 2012). DA can affect most if not all human immune cells, including T and B cells, dendritic cells, macrophages, microglia, neutrophils and NK cells, and it has been suggested that DA exerts mainly stimulatory effects on resting immune cells and inhibitory effects on activated immune cells (Sarkar et al 2010;Levite 2012). Immune cells themselves produce DA, which may act as autocrine/paracrine mediator on immune cells as well as on neighbouring cells (Bergquist and Silberring 1998;Cosentino et al 1999;Marino et al 1999;Cosentino et al 2000;Cosentino et al 2002a andb, Cosentino et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Expression of Dopaminergic Receptors on Human CD4+ T Lymphocytes: Flow Cytometric Analysis of Naive and Memory Subsets and Relevance for the Neuroimmunology of Neurodegenerative Disease

Kuštrimović

Rasini

Legnaro

et al. 2014

J Neuroimmune Pharmacol

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Dopamine (DA) is a crucial transmitter in the neuroimmune network, where it contributes to the nervous system-immune system interplay as well as in the communication among immune cells. DA acts through five different dopaminergic receptors (DR) grouped into two families: the D1-like (D1 and D5) and the D2-like (D2, D3 and D4). By use of 5-color flow cytometric analysis, we examined the expression of DR on human CD4+ naive T lymphocytes (CD3+CD4+CD45RA+CCR7+), central memory (TCM, CD3+CD4+CD45RA-CCR7+) and effector memory T cells (TEM, CD3+CD4+CD45RA-CCR7-). In addition, in cultured CD4+ T cells we investigated the changes in DR expression induced by stimulation with antiCD3/antiCD28 antibodies. Results showed that CD4+ T cells always expressed all the five DR: D1-like DR were identified on average on 11.6-13.1 % and D2-like DR on 3.1-8.1 % of the cells. DR on CD4+ naive T cells, TCM, and TEM had distinct expression patterns: naive T cells expressed more D1-like than D2-like DR, which on the contrary were increased in TCM and TEM cells. In cultured CD4+ T cells stimulation with anti-CD3/anti-CD28 antibodies increased the expression of D1-like DR by 71-84 % and of D2-like DR by 55-97 %. The frequency of DR was higher in apoptotic cells in comparison to viable cells, however stimulation increased all DR on viable cells, without affecting their expression on apoptotic cells. The present results contribute to unravel the complexity of dopaminergic pathways in human CD4+ T lymphocytes, suggesting their involvement in memory functions as well as in apoptotic processes. In view of the role of CD4+ memory T cells in neuroinflammation and neurodegeneration during Parkinson's disease, the relevance of these findings must be assessed in the clinical setting.

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Dopamine in the Immune System: Dopamine Receptors in Immune Cells, Potent Effects, Endogenous Production and Involvement in Immune and Neuropsychiatric Diseases

Cited by 24 publications

References 98 publications

The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

Expression of Dopaminergic Receptors on Human CD4+ T Lymphocytes: Flow Cytometric Analysis of Naive and Memory Subsets and Relevance for the Neuroimmunology of Neurodegenerative Disease

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