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

Joanna Mikulak, Luisa Bozzo, Alessandra Roberto, Elena Pontarini, Paolo Tentorio, Kelly Hudspeth, Enrico Lugli, Domenico Mavilio

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish
Pages (from-to)2792-2800
Number of pages9
JournalJournal of Immunology
Volume193
Issue number6
DOIs
Publication statusPublished - Sep 15 2014

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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