Atorvastatin induces T cell anergy via phosphorylation of ERK1

被引:44
作者
Waiczies, S
Prozorovski, T
Infante-Duarte, C
Hahner, A
Aktas, O
Ullrich, O
Zipp, F
机构
[1] Univ Hosp Charite, Neurowissensch Forschungszentrum 2680, Inst Neuroimmunol, D-10098 Berlin, Germany
[2] Univ Hosp Magdeburg, Inst Immunol, Magdeburg, Germany
关键词
D O I
10.4049/jimmunol.174.9.5630
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Modulation of T cell response is a novel property of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors. Previously we reported the benefits of atorvastatin treatment in experimental autoimmune encephalomyelitis, the murine model of the T cellmediated autoimmune disorder multiple sclerosis, in which a blockade of the T cell cycle by atorvastatin was attributed to an accumulation of the negative regulator p27(Kip1). We show in this report that, in line with the documented role of p27(Kip1) in T cell anergy, treatment with atorvastatin results in a deficient response to a second productive stimulus in human T cells. This effect of atorvastatin was dependent on HMG-CoA reduction and required-IL-10 signaling. Importantly, atorvastatin induced an early and sustained phosphorylation of ERK1, but not ERK2, which was crucial for the induction of anergy. On the basis of the therapeutic impact of HMG-CoA reductase inhibitors, the present findings should pave the way for future therapeutic concepts related to tolerance induction in neuroinflammatory disorders such as multiple sclerosis.
引用
收藏
页码:5630 / 5635
页数:6
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