Helmholtz Gemeinschaft


Modulating T cell signaling cascades by HMG-CoA reductase inhibitors

Item Type:Review
Title:Modulating T cell signaling cascades by HMG-CoA reductase inhibitors
Creators Name:Waiczies, S., Prozorovski, T. and Zipp, F.
Abstract:The modulation of undesirable immune responses is a novel and exciting property of statins. These drugs were initially designed to lower lipid levels by specifically inhibiting the rate-limiting enzyme HMGCR (3-hydroxy-3- methylglutaryl (HMG)-CoA reductase; EC; standard protein abbreviation HMG-CoA reductase), which is important for cholesterol synthesis. Various mechanisms accounting for the anti-inflammatory properties of statins have been proposed: preliminary studies reported an interference in MHC class II presentation necessary for transmitting antigen-specific signals to T cells but subsequently a direct impact on various intracellular T cell molecules independent of antigen presentation or T cell receptor triggering was also reported. Several groups including ours have recently reported the benefits of treating various animal models of T cell-mediated autoimmune disorders such as multiple sclerosis and rheumatoid arthritis with HMGCR inhibitors. Although a plethora of molecular processes have been reported, the main biological alterations responsible for modulating T cell response by statins involve (I) a direct interference in T cell cycle progression and induction of anergy and (II) a shift in the differentiation status of T-helper (Th) effector cells towards a regulatory phenotype. The impact of statins on the T cellular immune response is discussed here in detail.
Keywords:HMG-CoA Reductase, Statins, T Helper Cell, Cell Cycle, Anergy
Source:Signal Transduction
Page Range:231-244
Date:October 2005
Official Publication:https://doi.org/10.1002/sita.200500058

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