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首页> 外文期刊>Signal transduction: Receptors, mediators and genes: Official journal of the Signal Transduction Society >Modulating T cell signaling cascades by HMG-CoA reductase inhibitors
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Modulating T cell signaling cascades by HMG-CoA reductase inhibitors

机译：通过HMG-CoA还原酶抑制剂调节T细胞信号转导级联

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摘要

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.
机译：不良免疫反应的调节是他汀类药物的一种新颖而令人兴奋的特性。这些药物最初设计为通过特异性抑制限速酶HMGCR（3-羟基-3-甲基戊二酰（HMG）-CoA还原酶; EC 1.1.1.88;标准蛋白质缩写HMG-CoA还原酶）来降低脂质水平。用于胆固醇合成。已经提出了解释他汀类药物抗炎特性的各种机制：初步研究报告了干扰MHC II类递呈的必要条件，该递呈是将抗原特异性信号传递给T细胞所必需的，但随后直接影响各种细胞内T细胞分子，而与抗原递呈无关或T细胞受体触发的报道。包括我们在内的几个小组最近报告了用HMGCR抑制剂治疗T细胞介导的自身免疫性疾病（例如多发性硬化症和类风湿性关节炎）的各种动物模型的益处。尽管已经报道了许多分子过程，但负责他汀类药物调节T细胞反应的主要生物学变化涉及（I）直接干扰T细胞周期进程和诱发无能，以及（II）T分化状态的转变-辅助（Th）效应细胞趋向于调节表型。他汀类药物对T细胞免疫反应的影响在这里详细讨论。

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