Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals.
Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals.
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DOI：
10.1155/2015/762506
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发表时间：
2015
影响因子：
4.1
通讯作者：
Velilla PA
中科院分区：
文献类型：
--
作者：
Rodríguez-Perea AL;Montoya CJ;Olek S;Chougnet CA;Velilla PA
他汀类药物已被证明在炎症条件下调节CD 4 + FOXP 3 + T细胞（Treg）的数量和抑制功能。然而，他汀类药物是否也可以在没有炎症的情况下影响Treg还没有很好地确定。为了解决这个问题，18名胆固醇正常的男性受试者每天接受洛伐他汀或阿托伐他汀治疗，持续45天。在第0、7、30和45天评价循环Treg的频率和表型。在CD 4 + T细胞中测量FOXP 3、IDO、TGF-β和IL-10的mRNA水平。我们发现两种他汀类药物在第30天显著增加Treg频率和FOXP 3 mRNA水平。在第45天，Treg数量恢复到基线值;然而，TGF-β和FOXP 3 mRNA水平仍然很高，伴随着表达CTLA-4和GITR的Treg的百分比增加。他汀类药物治疗后Treg Ki-67表达降低。Treg频率与血浆高密度脂蛋白胆固醇（HDL-c）水平呈正相关，表明HDL-c在Treg稳态中的作用。因此，他汀类药物似乎具有非炎症依赖性免疫调节作用。因此，Treg细胞频率的增加可能有助于他汀类药物的免疫调节作用，即使在健康个体中也是如此。
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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