Dopamine favors expansion of glucocorticoid-resistant IL-17-producing T cells in multiple sclerosis |
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| Affiliation: | 1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;2. Post-graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;3. Department of General Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;4. Department of Microbiology, Immunology and Parasitology, State University of Rio de Janeiro, Rio de Janeiro, Brazil;1. Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea;2. Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, South Korea;3. Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea;4. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea;5. Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, South Korea;1. Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, China;2. School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK;1. Division of Transcranial Doppler Ultrasound, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;2. Division of Ophthalmology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;3. Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;4. Division of Neurology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;5. Department of Anatomy and Regenerative Biology, The George Washington University, 2300 Eye Street, NW Washington DC 20037, USA;6. Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China |
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| 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 [3H]-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. |
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| Keywords: | Multiple sclerosis Dopamine Lipopolysaccharide Cytokines Th17 IL-10 T cells |
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