Circulating regulatory T cells in adult-onset Still's disease: Focusing on their plasticity and stability

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)-gamma, 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-gamma, IL-17 and IL-4 in T-regs were significantly increased in patients with acute AOSD. IFN-gamma 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-gamma 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.

Automated summary

In AOSD, regulatory T cells (T-regs) show reduced proportion and functional activity, and altered cytokine expression levels during acute phase, indicating plastic changes. However, these aberrant findings in T-regs are significantly improved after remission, suggesting a restoration of T-reg stability. IFN-gamma and IL-4 expression levels in T-regs may be associated with disease severity, while down-regulation of FoxP3 may be related to IL-17 expression in T-regs.