title: Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals.
abstract: Statins have been shown to modulate the number and the suppressive function of CD4(+)FOXP3(+) T cells (Treg) in inflammatory conditions. However, it is not well established whether statin could also affect Treg in absence of inflammation. To address this question, eighteen normocholesterolemic male subjects were treated with lovastatin or atorvastatin daily for 45 days. The frequency and phenotype of circulating Treg were evaluated at days 0, 7, 30, and 45. mRNA levels of FOXP3, IDO, TGF-β, and IL-10 were measured in CD4(+) T cells. We found that both statins significantly increased Treg frequency and FOXP3 mRNA levels at day 30. At day 45, Treg numbers returned to baseline values; however, TGF-β and FOXP3 mRNA levels remained high, accompanied by increased percentages of CTLA-4- and GITR-expressing Treg. Treg Ki-67 expression was decreased upon statin treatment. Treg frequency positively correlated with plasma levels of high-density lipoprotein cholesterol (HDL-c), suggesting a role for HDL-c in Treg homeostasis. Therefore, statins appear to have inflammation-independent immune-modulatory effects. Thus, the increase in Treg cells frequency likely contributes to immunomodulatory effect of statins, even in healthy individuals.
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: Rodríguez-Perea
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Montoya
authors.affiliation: Epiontis GmbH, 12489 Berlin, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.affiliation: Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Velilla
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D008076:Cholesterol, HDL / Q000097:blood; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016130:Immunophenotyping; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids