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)-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.
(© 2021 British Society for Immunology.)