Dysregulated ICOS⁺ proinflammatory and suppressive regulatory T cells in patients with rheumatoid arthritis

Regulatory T cells (Tregs) serve an important role in the pathogenesis of rheumatoid arthritis (RA) by regulating autoimmunity and inflammation. Humans and mice contain inducible T-cell costimulator-positive (ICOS⁺) Tregs, although their role in RA is unclear. A total of 33 patients with RA and 17 normal control (NC) subjects were examined. The proportion of ICOS⁺ Tregs in the peripheral blood and intracellular cytokine levels in these cells were assessed using flow cytometry. The percentage of ICOS⁺ Tregs increased in the cohort of patients with RA compared with the NCs. Such increases were much larger in patients with inactive RA compared with patients with active RA. Additionally, ICOS⁺ Tregs expressed multiple suppressive cytokines, including interleukin (IL)-10, transforming growth factor-β and IL-35, but expressed low levels of IL-17. Importantly, the expression of suppressive cytokines in ICOS⁺ Tregs from patients with active RA decreased, but IL-17 expression noticeably increased compared with patients with inactive RA. The present findings suggested that ICOS⁺ Tregs may perform inflammatory and inhibitory functions, and abnormal ICOS⁺ Tregs numbers and functions may contribute to the pathogenesis of RA.