Imbalance between regulatory T cells and Th17 cells in patients with systemic sclerosis

Abstract

Objective To investigate the levels, phenotypes and functions of regulatory T cells (Treg) and Th17 cells in systemic sclerosis (SSc) patients and assess the role of imbalance between Treg and Th17 cells in the pathogenesis of SSc. Methods Peripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, the cytotoxic T-lymphocyte antigen-4 (CTLA-4), FoxP3, and IL-17 using flow cytometry. Treg immunosuppression capacities were measured in co-cultured experiments. The expressions of IL-17A, IL-22, IL-6 and IL-1β were measured by FlowcytoMix. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA were measured by real-time polymerase chain reaction (PCR). The independent samples t-test was used to compare data between the groups. Results The frequency of Treg cells was significantly elevated in SSc [(3.6±1.1)%] compared with controls [(2.0±0.8)%, t=6.88, P<0.01)] and the expression of CTLA-4 was lower in Treg cells of SSc (P=0.034). The expression of CTLA-4 and FoxP3 mRNA was lower in SSc compared with controls(P<0.05), the immunosuppressive capacity of Treg cells were diminished in SSc (P=0.034). Th17 cells were increased in SSc (P<0.01); the levels of IL-17A, IL-22, IL-6 and IL-1β in the serums of SSc were higher than the controls(P<0.05). In SSc, CD25+FoxP3+IL-17+ cells were increased [0.075%±0.032)% vs (0.049±0.027)%, t=3.52, P=0.029], but no difference of CD25+FoxP3+IL-17- was observed when compared with control. The expression of IL-17A and RORC mRNA were increased in SSc (P<0.01, respectively). Conclusion Both Treg and Th17 cells are increased in patients of SSc. Treg increases along with the deficiency of phenotype and function. FoxP3+IL-17+ co-express cells are increased, and the balance between Treg and Th17 cells is broken. Key words: Scleroderma, systemic; T-lymphocytes; Interleukin-17; FoxP3