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Atorvastatin induces T cell anergy via phosphorylation of ERK1

Item Type:Article
Title:Atorvastatin induces T cell anergy via phosphorylation of ERK1
Creators Name:Waiczies, S., Prozorovski, T., Infante-Duarte, C., Hahner, A., Aktas, O., Ullrich, O. and Zipp, F.
Abstract: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 cell-mediated 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.
Keywords:Atorvastatin, Butadienes, Cell Line, Clonal Anergy, Heptanoic Acids, Immunologic Adjuvants, Interleukin-10, MAP Kinase Kinase 1, MAP Kinase Kinase 2, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Nitriles, Phosphorylation, Protein Kinase Inhibitors, Pyrroles, T-Lymphocytes, Time Factors
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists
Volume:174
Number:9
Page Range:5630-5635
Date:1 May 2005
Official Publication:https://doi.org/10.4049/jimmunol.174.9.5630
PubMed:View item in PubMed

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