We investigated the characteristics of regulatory T cells in adult-onset Still’s disease (AOSD) with a focus on their plasticity, stability and relationship to disease severity. The proportion of circulating CD4⁺CD25⁺forkhead box protein 3 (FoxP3⁺) cells (T_regs) and intracellular expression of effector cytokines, including interferon (IFN)-γ, interleukin (IL)-17 and IL-4, was analysed in 27 untreated patients with AOSD (acute AOSD), 11 of the 27 patients after remission and 16 healthy controls (HC) using flow cytometry. The suppressive ability of T_regs was also evaluated. Regression analyses of the results were performed. The proportion of T_regs was significantly lower in patients with acute AOSD than in the HC. The expression levels of IFN-γ, IL-17 and IL-4 in T_regs were significantly increased in patients with acute AOSD. IFN-γ and IL-4 expression levels were inversely correlated with the proportion of T_regs and positively correlated with serum ferritin levels. Decreased expression of FoxP3 in CD4⁺CD25⁺ cells, which was correlated with increased expression of IL-17, and impaired suppressive function were observed in T_regs in acute AOSD. However, these aberrant findings in T_regs, including the reduced circulating proportion and functional ability and altered intracellular expression levels of cytokines and FoxP3, were significantly improved after remission. In acute AOSD, T_regs show plastic changes, including effector cytokine production and reductions in their proportion and functional activity. IFN-γ and IL-4 expression levels in T_regs may be associated with disease severity. Also, down-regulation of FoxP3 may be related to IL-17 expression in T_regs. Importantly, the stability of T_regs can be restored in remission.

中文翻译：

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成人斯蒂尔病中的循环调节性 T 细胞：关注它们的可塑性和稳定性

我们研究了成人斯蒂尔病 (AOSD) 中调节性 T 细胞的特征，重点是它们的可塑性、稳定性和与疾病严重程度的关系。^{在中分析了循环 CD4 +} CD25 ⁺叉头盒蛋白 3 (FoxP3 ⁺ ) 细胞 (T _regs )的比例和效应细胞因子的细胞内表达，包括干扰素 (IFN)-γ、白细胞介素 (IL)-17 和 IL-4。 27 名未经治疗的 AOSD（急性 AOSD）患者、27 名缓解后患者中的 11 名和 16 名健康对照（HC）使用流式细胞术。还评估了 T _regs的抑制能力。对结果进行回归分析。_{T regs}的比例急性 AOSD 患者的发病率明显低于 HC 患者。急性 AOSD 患者T _regs中 IFN-γ、IL-17 和 IL-4 的表达水平显着升高。_{IFN-γ和IL-4表达水平与T regs}的比例呈负相关，与血清铁蛋白水平呈正相关。CD4 ⁺ CD25 ⁺细胞中 FoxP3 的表达降低，这与 IL-17 的表达增加相关，并且在急性 AOSD的 T _regs中观察到抑制功能受损。然而，T _{regs中的这些异常发现}，包括降低的循环比例和功能能力以及改变的细胞因子和FoxP3的细胞内表达水平，在缓解后得到显着改善。在急性 AOSD 中，T _regs表现出可塑性变化，包括效应细胞因子的产生以及它们的比例和功能活性的降低。_{T regs}中的 IFN-γ 和 IL-4 表达水平可能与疾病严重程度有关。此外，FoxP3 的下调可能与 T _regs中的 IL-17 表达有关。_{重要的是，T regs}的稳定性可以在缓解期恢复。