title: Dopamine favors expansion of glucocorticoid-resistant IL-17-producing T cells in multiple sclerosis.
abstract: Dopamine (DA) is a neurotransmitter produced mainly in the central nervous system (CNS) that has immunomodulatory actions on T cells. As the multiple sclerosis (MS) has long been regarded as an autoimmune disease of CNS mediated by T cells, the objective of this study was to evaluate the impact of DA on in vitro functional status of T cells from relapsing-remitting (RR)-MS patients. Peripheral T-cells from RR-MS patients were activated by mitogens and cell proliferation and cytokine production were assayed by [(3)H]-thymidine uptake and ELISA, respectively. Our results demonstrated that DA enhanced in vitro T cell proliferation and Th17-related cytokines in MS-derived cell cultures. In addition, this catecholamine reduced Treg-related cytokines (IL-10 and TGF-β) release by activated CD4(+) T cells. These DA-induced effects on T cells were mainly dependent on IL-6 production by both polyclonally-activated CD4(+) T cells and LPS-stimulated monocytes. Furthermore, the production of IL-17 and IL-6 by MS-derived T cells was directly related with neurological disability (EDSS score), and the release of these cytokines was less sensitive to glucocorticoid inhibition in MS patients than in control group, mainly after DA addition. In conclusion, our data suggest that DA amplifies glucocorticoid-resistant Th17 phenotype in MS patients, and this phenomenon could be, at least in part, due to its ability to induce IL-6 production by monocytes and CD4(+) T cells.
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thais B
authors.initials: TB
authors.lastname: Ferreira
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Priscila O
authors.initials: PO
authors.lastname: Barros
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Teixeira
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Tatiane
authors.initials: T
authors.lastname: Cassano
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Newton
authors.initials: N
authors.lastname: Centurião
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Taissa M
authors.initials: TM
authors.lastname: Kasahara
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Joana
authors.initials: J
authors.lastname: Hygino
authors.affiliation: Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudia Cristina F
authors.initials: CC
authors.lastname: Vasconcelos
authors.affiliation: Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Helcio Alvarenga
authors.initials: HA
authors.lastname: Filho
authors.affiliation: Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Alvarenga
authors.affiliation: Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Wing
authors.affiliation: Department of General Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Regis M
authors.initials: RM
authors.lastname: Andrade
authors.affiliation: Department of Microbiology, Immunology and Parasitology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Arnaldo F
authors.initials: AF
authors.lastname: Andrade
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: cbento@unirio.br.
authors.forename: Cleonice A M
authors.initials: CA
authors.lastname: Bento
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D010835:Phytohemagglutinins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D004298:Dopamine
keywords: Cytokines; Dopamine; IL-10; Lipopolysaccharide; Multiple sclerosis; T cells; Th17