HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Waiczies, S. Articles by Zipp, F. Search for Related Content PubMed PubMed Citation Articles by Waiczies, S. Articles by Zipp, F.

Atorvastatin Induces T Cell Anergy via Phosphorylation of ERK1¹

Sonia Waiczies^*, Timour Prozorovski^*, Carmen Infante-Duarte^*, Astrid Hahner^*, Orhan Aktas^*, Oliver Ullrich and Frauke Zipp^2,*

^* Institute of Neuroimmunology, Neuroscience Research Center, University Hospital Charité, Berlin, Germany; and Institute of Immunology, University Hospital Magdeburg, Magdeburg, Germany

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.

This article has been cited by other articles:

				M. A. Kriegel, S. Adam-Klages, C. Gabler, N. Blank, M. Schiller, C. Scheidig, J. R. Kalden, and H.-M. Lorenz Anti-HLA-DR-triggered monocytes mediate in vitro T cell anergy Int. Immunol., April 1, 2008; 20(4): 601 - 613. [Abstract] [Full Text] [PDF]

				S. Waiczies, I. Bendix, and F. Zipp Geranylgeranylation but Not GTP-Loading of Rho GTPases Determines T Cell Function Sci. Signal., March 25, 2008; 1(12): pt3 - pt3. [Abstract] [Full Text] [PDF]

				S. Waiczies, I. Bendix, T. Prozorovski, M. Ratner, I. Nazarenko, C. F. Pfueller, A. U. Brandt, J. Herz, S. Brocke, O. Ullrich, et al. Geranylgeranylation but Not GTP Loading Determines Rho Migratory Function in T Cells J. Immunol., November 1, 2007; 179(9): 6024 - 6032. [Abstract] [Full Text] [PDF]

				E. C. Jury, D. A. Isenberg, C. Mauri, and M. R. Ehrenstein Atorvastatin Restores Lck Expression and Lipid Raft-Associated Signaling in T Cells from Patients with Systemic Lupus Erythematosus J. Immunol., November 15, 2006; 177(10): 7416 - 7422. [Abstract] [Full Text] [PDF]

				A. Agrawal, S. Dillon, T. L. Denning, and B. Pulendran ERK1-/- Mice Exhibit Th1 Cell Polarization and Increased Susceptibility to Experimental Autoimmune Encephalomyelitis J. Immunol., May 15, 2006; 176(10): 5788 - 5796. [Abstract] [Full Text] [PDF]