Dopaminergic Regulation of Innate Immunity: a Review

Abstract

Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson's disease. Comparatively little is known about DA and the innate immune response, although DA may affect innate immune system cells such as dendritic cells, macrophages, microglia, and neutrophils. The present review aims at providing a complete and exhaustive summary of currently available evidence about DA and innate immunity, and to become a reference for anyone potentially interested in the fields of immunology, neurosciences and pharmacology. A wide array of dopaminergic drugs is used in therapeutics for non-immune indications, such as Parkinson's disease, hyperprolactinemia, shock, hypertension, with a usually favorable therapeutic index, and they might be relatively easily repurposed for immune-mediated disease, thus leading to innovative treatments at low price, with benefit for patients as well as for the healthcare systems.

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

“…Microglia are major mediators in the immune response to CNS infection or tissue damage releasing a variety of cytokines upon activation (Mack et al, 2003; Davalos et al, 2005; Saijo, Crotti and Glass, 2013; Nayak et al, 2014). Their dysregulation has been implicated with many neurodegenerative diseases (Pinoli et al, 2017). …”

Role of peripheral dopaminergic system in the pathogenesis of experimental colitis in rats

“…Most recently described IBD susceptibility genes are linked to host immune system including epithelial barrier function, host defence mechanisms against pathogens as well as autophagy, innate and adaptive immune response [29]. IBD is characterized by upregulation of proinflammatory cytokines (TNF-α, interleukin (IL)-6, IL-13, IL-17, IL-18, and IL-21) and decrease of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) [30].…”

“…Mononuclear phagocytes are also critical in tissue restoration after injury, as well as in the initiation and resolution of innate and adaptive immune responses [30]. DA and dopaminergic agents can affect several functions of monocytes; for example, DA is able to decrease LPS-induced proliferation of human monocytes [37].…”

Differential Response of Dopamine Mediated by β-Adrenergic Receptors in Human Keratinocytes and Macrophages: Potential Implication in Wound Healing

“…Although dopamine is known for its role as a neurotransmitter, it has been described that this mediator can also modulate the immune response [1]. Cells of the cutaneous immune system express dopaminergic and ARs.…”

“…Dopamine is a key neurotransmitter connecting the nervous and the immune systems as well as a mediator produced and released by immune cells [1, 2]. It has been demonstrated that dopamine and catecholamines, adrenaline and noradrenaline, modulate proliferation, apoptosis, and cytokine production in immune cells [3, 4].…”