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

Abstract

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 (Tregs) 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 Tregs was also evaluated. Regression analyses of the results were performed. The proportion of Tregs was significantly lower in patients with acute AOSD than in the HC. The expression levels of IFN‐γ, IL‐17 and IL‐4 in Tregs were significantly increased in patients with acute AOSD. IFN‐γ and IL‐4 expression levels were inversely correlated with the proportion of Tregs 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 Tregs in acute AOSD. However, these aberrant findings in Tregs, 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, Tregs show plastic changes, including effector cytokine production and reductions in their proportion and functional activity. IFN‐γ and IL‐4 expression levels in Tregs may be associated with disease severity. Also, down‐regulation of FoxP3 may be related to IL‐17 expression in Tregs. Importantly, the stability of Tregs can be restored in remission.