Atorvastatin induces T cell anergy via phosphorylation of ERK1


  • S. Waiczies
  • T. Prozorovski
  • C. Infante-Duarte
  • A. Hahner
  • O. Aktas
  • O. Ullrich
  • F. Zipp


  • Journal of Immunology


  • J Immunol 174 (9): 5630-5635


  • 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.