Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.

Abstract

ObjectiveImmune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naïve SSc.MethodsPeripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR.ResultsThe frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, pConclusionA decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3(low)CD45RA(-) T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.