Th17 Cells/Regulatory T Cells Imbalance In Systemic Lupus Erythematosus

ObjectiveTo investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells, assess the expression of FoxP3 and CD25 on CD4+ regulatory T (Treg) cells and the expression of RORyt gene and FoxP3 gene, measure the level of Th cells related cytokines and their clinical significance in patients with systemic lupus erythematosus (SLE), evaluate the role of Th17 and Treg cells in the pathogenesis of patients with lupus nephritis (LN).MethodsA total of 60 systemic lupus erythematosus patients and 28 healthy controls were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry (FACS). The expression of CD25 and FoxP3 by CD4+ T cells was analyzed by flow cytometric analysis. RT-PCR was used to measure the expression of RORyt gene and FoxP3 gene. The concentrations of serum IL-17, IL-4, IFN-y, TGF-β1 and urinary TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA).Results1. A significant increase in the frequency of Th17 cells and a significant decrease in the frequency of CD4+CD25+、CD4+CD25high and CD4+CD25+FoxP3+ T cells in peripheral blood of LN patients compared with SLE group and healthy controls (P< 0.05, P<0.01; respectively). LN patients had a lower percentage and expression of FoxP3 in CD4+CD25high T cells than SLE patients without nephritis (P< 0.05).2. The expression of RORyt mRNA levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls (P< 0.05). The expression of FoxP3 mRNA levels in LN patients exhibited a significant decrease compared with healthy controls (P<0.05). 3. The concentration of serum IL-17, IL-4, IFN-y was found increased in LN patients compared with that from healthy controls (P< 0.001), while serum TGF-β1 was found decreased in SLE patients compared with that from healthy controls (P< 0.001). Urinary TGF-β1 levels were significantly higher in SLE patients with nephritis in comparison to those without nephritis and healthy controls (P<0.001), urinary TGF-β1 levels correlated positively with 24h urine protein (P<0.01).ConclusionsThe significantly elevated Th17 cells were accompanied by FoxP3+Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.