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Journal of Immunology Research
Volume 2015 (2015), Article ID 762506, 8 pages
http://dx.doi.org/10.1155/2015/762506
Research Article

Statins Increase the Frequency of Circulating CD4+FOXP3+ Regulatory T Cells in Healthy Individuals

1Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia
2Epiontis GmbH, 12489 Berlin, Germany
3Division of Immunobiology, Department of Pediatrics, Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH 45229, USA

Received 3 December 2014; Accepted 8 February 2015

Academic Editor: Hiroshi Nakajima

Copyright © 2015 Ana Lucía Rodríguez-Perea et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.