Role of T helper 17 cells in the pathogenesis of systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that occurs in genetically prone individuals. Autoimmunity could not be simply explained by Th1/Th2 cell paradigm. T helper 17(Th17) cells producing the cytokine interleukin-17 (IL-17) may explain the promotion and progression of autoimmune phenomena. This study aimed to investigate the role of Th17cells, IL-17 and interleukin-23 (IL-23) in the pathogenesis of SLE and their correlation with disease activity. The frequencies of circulating Th17 cells in 15 patients with active SLE, 15 patients with inactive disease and 15 healthy control subjects were measured using Flowcytometry after stimulation with phorbol myristate acetate (PMA) and ionomycin for 4 hours. Serum levels of IL-17 and IL-23 were measured using the enzyme linked immunosorbent assay (ELISA). Significantly higher mean frequencies of circulating Th17 cells were found in active SLE patients (1.54 +/- 0.38%, P < 0.001) and inactive SLE patients (1.23 +/- 0.25%, P = 0.009) compared to the control group (0.88 +/- 0.41%). The frequencies of circulating Th17 cells positively correlated with the SLEDAI score (r = 0.812, P < 0.001). The serum levels of IL-17 and IL-23 were significantly higher in active SLE (P < 0.001) and inactive SLE patients (P < 0.001) than the control group while, serum levels of both cytokines correlated positively with SLEDAI score (r = 0.661, P < 0.01 and r = 0.701, P < 0.01 respectively). There was significant positive correlation between the frequency of circulating Th17 cells and plasma levels of IL-17 and IL-23 (r = 0.789, P < 0.001) and (r = 0.792, P < 0.001) respectively. Results of this study provides evidence of a role of Th17 cells in the pathogenesis of SLE, and offer scientific rationale for the utility of Th17 cells, IL-17 and IL-23 as biological markers for SLE disease activity. This would raise the possibility of anti-IL-17 and anti-IL-23 as innovative therapeutic options in controlling disease activity of SLE.