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-γ. The inhibition of IFN-γ 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-γ. 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.
Dopamine inhibits the effector functions of activated NK cells via the upregulation of the D5 receptor / J. Mikulak, L. Bozzo, A. Roberto, E. Pontarini, P. Tentorio, K. Hudspeth, E. Lugli, D. Mavilio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 193:6(2014 Sep), pp. 2792-2800.
|Titolo:||Dopamine inhibits the effector functions of activated NK cells via the upregulation of the D5 receptor|
MAVILIO, DOMENICO (Corresponding)
|Parole Chiave:||Cell Line, Tumor; Cell Proliferation; Cytotoxicity, Immunologic; Dopamine; HEK293 Cells; Humans; Inflammation; Interferon-gamma; Interleukin-2; Killer Cells, Natural; Lymphocyte Activation; MicroRNAs; NF-kappa B p50 Subunit; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-rel; Receptors, Dopamine D5; Recombinant Proteins; Up-Regulation; Immunology; Medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio|
Settore MED/04 - Patologia Generale
Settore MED/26 - Neurologia
|Data di pubblicazione:||set-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4049/jimmunol.1401114|
|Appare nelle tipologie:||01 - Articolo su periodico|