The discovery of FOXP3⁺ regulatory T (T_reg) cells as a distinct cell lineage with a central role in regulating immune responses provided a deeper understanding of self-tolerance. The transcription factor FOXP3 serves a key role in T_reg cell lineage determination and maintenance, but is not sufficient to enable the full potential of T_reg cell suppression, indicating that other factors orchestrate the fine-tuning of T_reg cell function. Moreover, FOXP3-independent mechanisms have recently been shown to contribute to T_reg cell dysfunction. FOXP3 mutations in humans cause lethal fulminant systemic autoinflammation (IPEX syndrome). However, it remains unclear to what degree T_reg cell dysfunction is contributing to the pathophysiology of common autoimmune diseases. In this Review, we discuss the origins of T_reg cells in the periphery and the multilayered mechanisms by which T_reg cells are induced, as well as the FOXP3-dependent and FOXP3-independent cellular programmes that maintain the suppressive function of T_reg cells in humans and mice. Further, we examine evidence for T_reg cell dysfunction in the context of common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis.

^{FOXP3 +}调节性 T (T _reg ) 细胞作为一种独特的细胞谱系，在调节免疫反应中发挥核心作用，这一发现让我们对自我耐受有了更深入的了解。转录因子 FOXP3 在 T _reg细胞谱系确定和维持中发挥关键作用，但不足以充分发挥 T _reg细胞抑制的潜力，表明其他因子协调 T _reg细胞功能的微调。此外，FOXP3 独立机制最近已被证明会导致 T _reg细胞功能障碍。人类 FOXP3 突变会导致致命的暴发性全身性自身炎症（IPEX 综合征）。然而，目前尚不清楚 T _reg细胞功能障碍在多大程度上导致常见自身免疫性疾病的病理生理学。在这篇综述中，我们讨论了外周T _reg细胞的起源和诱导 T _reg细胞的多层机制，以及维持 T _reg细胞抑制功能的 FOXP3 依赖和 FOXP3 独立细胞程序。人类和老鼠。此外，我们还检查了常见自身免疫性疾病（如多发性硬化症、炎症性肠病、系统性红斑狼疮和类风湿性关节炎）中T _{reg细胞功能障碍的证据。}