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FoxP3+ CD4+ T cells in systemic autoimmune diseases: the delicate balance between true regulatory T cells and effector Th-17 cells.

机译:系统性自身免疫性疾病中的FoxP3 + CD4 + T细胞:真正的调节性T细胞和效应Th-17细胞之间的微妙平衡。

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摘要

Breakdown of tolerance is a hallmark of autoimmune diseases. Over the past 10 years, there has been increased interest in the role of FoxP3(+) regulatory T cells (T(Regs)) in maintaining peripheral tolerance. Dysfunction of these cells is considered to play a major role in the development of autoimmune diseases. Besides their suppressive function, a fraction of these cells has the capacity to differentiate into IL-17-producing cells (Th-17), a phenomenon associated with autoimmune inflammation. The revealed plasticity of T(Regs), therefore, has obvious implications when designing therapeutic strategies for restoring tolerance in autoimmune diseases using T(Regs). In this review, we discuss development, classification, molecular characterization and mechanisms of suppression by T(Regs). In addition, we describe recent data on their potential conversion into Th-17 cells in human systemic autoimmune diseases. We also outline a new strategy for T(Reg)-based therapy via isolation, expansion and re-infusion of highly pure FoxP3(+) T(Regs) free of contaminating effector T cells.
机译:耐受性下降是自身免疫性疾病的标志。在过去的十年中,人们对FoxP3(+)调节性T细胞(T(Regs))在维持外周耐受性中的作用越来越感兴趣。这些细胞的功能障碍被认为在自身免疫疾病的发展中起主要作用。除了抑制功能外,这些细胞中的一部分还具有分化为IL-17产生细胞(Th-17)的能力,这是一种与自身免疫炎症相关的现象。因此,在设计使用T(Regs)恢复自身免疫性疾病耐受性的治疗策略时,所揭示的T(Regs)可塑性具有明显的意义。在这篇综述中,我们讨论了T(Regs)抑制的发展,分类,分子表征和机制。此外,我们描述了它们在人类系统性自身免疫性疾病中潜在转化为Th-17细胞的最新数据。我们还概述了通过高纯度的FoxP3(+)T(Regs)的分离,扩展和重新输注而不含污染性效应T细胞的基于T(Reg)疗法的新策略。

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