Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals

Journal of Immunology Research
Ana Lucía Rodríguez-PereaPaula Andrea Velilla

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.

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Citations

Apr 29, 2016·Clinical and Experimental Immunology·A L Rodríguez-PereaP A Velilla
Apr 6, 2017·Journal of Lipid Research·Cesar M RuedaClaire A Chougnet
Dec 30, 2017·Npj Aging and Mechanisms of Disease·Giuseppe Del GiudiceT Mark Doherty
Jan 15, 2019·Clinical and Experimental Immunology·A L Rodríguez-PereaP A Velilla-Hernández
May 16, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Edith González-GuevaraJuan Carlos Martínez-Lazcano
Sep 12, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Ana Lucía Rodríguez-PereaPaula Andrea Velilla Hernández
Nov 6, 2018·Journal of Clinical Medicine·Mona PanahiSusanne Sattler
Nov 12, 2018·Auto- Immunity Highlights·Georgios K VasileiadisGeorgios M Hadjigeorgiou
Feb 16, 2018·PLoS Pathogens·Kim J HasenkrugUlf Dittmer
Apr 3, 2020·Antioxidants & Redox Signaling·Cassandra M Moshfegh, Adam J Case
Oct 12, 2017·European Heart Journal·Moneeza K SiddiquiUNKNOWN PREDICTION-ADR Consortium
Jan 29, 2021·Mediators of Inflammation·Feiyang CaiGuangjie Chen
Aug 11, 2021·Current Opinion in Lipidology·Grant BarkerSrinivasa Reddy
Sep 5, 2021·BMC Medical Genomics·Timothy A McCaffreyGeorges St Laurent

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Methods Mentioned

BETA
density gradient centrifugation
PCR
flow cytometry

Software Mentioned

FACSDiva

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