Dopaminergic inhibition of human neutrophils is exerted through D1‐like receptors and affected by bacterial infection

Marino, Franca; Pinoli, Monica; Rasini, Emanuela; Martini, Stefano De; Luini, Alessandra; Pulze, Laura; Gasperina, Daniela Dalla; Grossi, Paolo; Legnaro, Massimiliano; Ferrari, Marco; Congiu, Terenzio; Pacheco, Rodrigo; Osorio‐Barrios, Francisco; Eguileor, Magda de; Cosentino, Marco

doi:10.1111/imm.13550

Cited by 6 publications

(6 citation statements)

References 59 publications

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“…These data suggest that dopamine generally inhibits the production of ROS and oxidative bursts in neutrophils, particularly at higher levels. This is supported by recent data showing exposure to dopamine (10 −6 –10 −9 M) broadly inhibited neutrophil activity in a D1-dependent manner ( Marino et al, 2022 ). Further, data from hypertension studies showing that the activation of D1-like receptors, particularly D5, reduced the production of ROS in mitochondria through an autophagy-associated mechanism ( Yang et al, 2006 ; Lee et al, 2021 ).…”

Section: Dopamine and Immune Cellssupporting

confidence: 84%

Dopamine, Immunity, and Disease

et al. 2022

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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.

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Section: Dopamine and Immune Cellssupporting

confidence: 84%

Dopamine, Immunity, and Disease

et al. 2022

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“…Although the present data suggest that the anti-inflammatory effects of SKF may be mainly mediated through D1-like receptors in the brain, they may also be at least partly attributed to peripheral effects because D1R is widely expressed by several types of leukocytes, 52 in which D1R activation may inhibit NLRP3 inflammasomes. 53 The expression of D1R in human and murine polymorphonuclear cells has been reported, 54 and a D1-like agonist has been shown to inhibit cell migration and ROS production. Furthermore, it is argued that DA is generated in the peripheral organs, including the lungs, affecting the immunological responses in these organs.…”

Section: Discussionmentioning

confidence: 99%

A dopamine D1-like receptor-specific agonist improves the survival of septic mice

Tanaka,

Choudhury,

Kikuchi

et al. 2024

iScience

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“…In addition, a previous work addressing the effect of DRD3 stimulation in the function of NK cells provided pharmacologic evidence indicating that DRD3 signalling inhibits the cytotoxic activity of splenic NK cells in vitro [ 43 ]. Additionally, recent research has shown pharmacologic and genetic evidence indicating that signalling through the high-affinity receptor DRD5 attenuates neutrophil migration towards the infection site [ 44 ]. Therefore, the general hypothesis that low/high-affinity dopamine receptors mediate anti/pro-inflammatory mechanisms does not always work.…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model

Chovar-Vera

López

Gálvez-Cancino

et al. 2022

Cells

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Dopamine has emerged as an important regulator of immunity. Recent evidence has shown that signalling through low-affinity dopamine receptors exerts anti-inflammatory effects, whilst stimulation of high-affinity dopamine receptors potentiates immunity in different models. However, the dopaminergic regulation of CD8+ T-cells in anti-tumour immunity remains poorly explored. Here, we studied the role of dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in the function of CD8+ T-cells and its consequences in the anti-tumour immune response. We observed that the deficiency of Drd3 (the gene encoding DRD3) in CD8+ T-cells limits their in vivo expansion, leading to an impaired anti-tumour response in a mouse melanoma model. Mechanistic analyses suggest that DRD3 stimulation favours the production of interleukin 2 (IL-2) and the surface expression of CD25, the α-chain IL-2 receptor, which are required for expansion and effector differentiation of CD8+ T-cells. Thus, our results provide genetic and pharmacologic evidence indicating that DRD3 favours the production of IL-2 by CD8+ T-cells, which is associated with higher expansion and acquisition of effector function of these cells, promoting a more potent anti-tumour response in a melanoma mouse model. These findings contribute to understanding how dopaminergic signalling affects the cellular immune response and represent an opportunity to improve melanoma therapy.

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Dopaminergic inhibition of human neutrophils is exerted through D1‐like receptors and affected by bacterial infection

Cited by 6 publications

References 59 publications

Dopamine, Immunity, and Disease

Dopamine, Immunity, and Disease

A dopamine D1-like receptor-specific agonist improves the survival of septic mice

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model

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