title: Fingolimod increases CD39-expressing regulatory T cells in multiple sclerosis patients.
abstract: BACKGROUND
  Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients.
  
  
  RESULTS
  Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start. mRNA expression was assessed in ex vivo PBMCs. The proportions of CD8, B cells, CD4 and CD39-expressing cells were analysed by flow cytometry. Treg proportion was quantified by flow cytometry and methylation-specific qPCR. Fingolimod treatment increased mRNA levels of CD39, AHR and CYP1B1 but decreased mRNA expression of IL-17, IL-22 and FOXP3 mRNA in PBMCs. B cells, CD4+ cells and Treg proportions were significantly reduced by this treatment, but remaining CD4+ T cells were enriched in FOXP3+ cells and in CD39-expressing Tregs.
  
  
  CONCLUSIONS
  In addition to the decrease in circulating CD4+ T cells and CD19+ B cells, our findings highlight additional immunoregulatory mechanisms induced by fingolimod.
authors.affiliation: Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Muls
authors.affiliation: Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Hong Anh
authors.initials: HA
authors.lastname: Dang
authors.affiliation: Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium; Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Christian J M
authors.initials: CJ
authors.lastname: Sindic
authors.affiliation: Neurochemistry Unit, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium; Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: van Pesch
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D001081:Apyrase / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D001081:Apyrase; D051792:Basic Helix-Loop-Helix Proteins; D065633:Cytochrome P-450 CYP1B1; D016207:Cytokines; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C585496:CYP1B1 protein, human; C067869:CD39 antigen