NDLI: Dopamine inhibits the effector functions of activated NK cells via the upregulation of the D5 receptor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bozzo, Luisa Mavilio, Domenico Tentorio, Paolo Pontarini, Elena Hudspeth, Kelly Roberto, Alessandra Mikulak, Joanna Lugli, Enrico
Description	Author Affiliation: Mikulak J ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Bozzo L ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Roberto A ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Pontarini E ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Tentorio P ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Hudspeth K ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Lugli E ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy); Mavilio D ( Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy)
Abstract	Several lines of evidence indicate that dopamine (DA) plays a key role in the cross-talk between the nervous and immune systems. In this study, we disclose a novel immune-regulatory role for DA: inhibition of effector functions of activated NK lymphocytes via the selective upregulation of the D5 dopaminergic receptor in response to prolonged cell stimulation with rIL-2. Indeed, engagement of this D1-like inhibitory receptor following binding with DA suppresses NK cell proliferation and synthesis of IFN-Î³. The inhibition of IFN-Î³ production occurs through blocking the repressor activity of the p50/c-REL dimer of the NF-κB complex. Indeed, the stimulation of the D5 receptor on rIL-2-activated NK cells inhibits the binding of p50 to the microRNA 29a promoter, thus inducing a de novo synthesis of this miRNA. In turn, the increased levels of microRNA 29a were inversely correlated with the ability of NK cells to produce IFN-Î³. Taken together, our findings demonstrated that DA switches off activated NK cells, thus representing a checkpoint exerted by the nervous system to control the reactivity of these innate immune effectors in response to activation stimuli and to avoid the establishment of chronic and pathologic inflammatory processes.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dopamine Immunology Interferon-gamma Biosynthesis Killer Cells, Natural Micrornas Receptors, Dopamine D5 Cell Line, Tumor Cell Proliferation Cytotoxicity, Immunologic Hek293 Cells Inflammation Interleukin-2 Pharmacology Lymphocyte Activation Genetics Nf-kappa B P50 Subunit Antagonists & Inhibitors Promoter Regions, Genetic Protein Binding Proto-oncogene Proteins C-rel Recombinant Proteins Up-regulation Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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