The immunosuppressive function of regulatory T (T_reg) cells is dependent on continuous expression of the transcription factor Foxp3. Foxp3 loss of function or induced ablation of T_reg cells results in a fatal autoimmune disease featuring all known types of inflammatory responses with every manifestation stemming from T_reg cell paucity, highlighting a vital function of T_reg cells in preventing fatal autoimmune inflammation. However, a major question remains whether T_reg cells can persist and effectively exert their function in a disease state, where a broad spectrum of inflammatory mediators can either inactivate T_reg cells or render innate and adaptive pro-inflammatory effector cells insensitive to suppression. By reinstating Foxp3 protein expression and suppressor function in cells expressing a reversible Foxp3 null allele in severely diseased mice, we found that the resulting single pool of rescued T_reg cells normalized immune activation, quelled severe tissue inflammation, reversed fatal autoimmune disease and provided long-term protection against them. Thus, T_reg cells are functional in settings of established broad-spectrum systemic inflammation and are capable of affording sustained reset of immune homeostasis.

调节性 T (T _reg ) 细胞的免疫抑制功能依赖于转录因子 Foxp3 的持续表达。Foxp3功能丧失或 T _reg细胞诱导消融导致致命的自身免疫性疾病，具有所有已知类型的炎症反应，每种表现都源于 T _reg细胞缺乏，突出了 T _reg细胞在预防致命性自身免疫性炎症中的重要功能。然而，一个主要问题仍然是 T _reg细胞是否可以在疾病状态下持续存在并有效发挥其功能，其中广谱的炎症介质可以使 T _reg失活细胞或使先天性和适应性促炎效应细胞对抑制不敏感。通过在严重疾病小鼠中恢复表达可逆Foxp3无效等位基因的细胞中的 Foxp3 蛋白表达和抑制功能，我们发现由此产生的单个获救 T _reg细胞池使免疫激活正常化，平息严重的组织炎症，逆转致命的自身免疫性疾病并提供长期对他们的长期保护。因此，T _reg细胞在已建立的广谱全身炎症环境中发挥作用，并能够提供免疫稳态的持续重置。