Modulating T cell signaling cascades by HMG-CoA reductase inhibitors

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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 1.1.1.88; 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
ISSN:	1615-4053
Publisher:	Wiley-VCH
Volume:	5
Number:	5
Page Range:	231-244
Date:	October 2005
Official Publication:	https://doi.org/10.1002/sita.200500058

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