Type I interferon and T helper 17 cells co-exist and co-regulate disease pathogenesis in lupus patients

T-helper 17 cells (Th17) and type I interferon (IFN-I) play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies have suggested that IFN-I suppresses Th17 development under autoimmune settings. Therefore, the main objective of this study was to define the association between IFN-I and Th17 pathways in SLE.

Peripheral blood samples and disease activity measures were collected from 31 patients fulfilling the American College of Rheumatology revised criteria for SLE. Serum was evaluated for IFN-α bioactivity and interleukin (IL)-6 levels by cell-based bioluminescence assay and enzyme-linked immunosorbent assay, respectively. The frequency of Th17 cells in peripheral blood was determined by intracellular cytokine staining for IL-17.

IFN-α bioactivity in the serum of lupus subjects (mean ± SD: 6.510 ± 3.686) was significantly higher (P = 0.001) compared to healthy controls (2.9 ± 1.061). Additionally, 58.1% and 41.9% of SLE subjects displayed high and low IFN-α bioactivity, respectively. We observed a significant increase (P = 0.04) in the percentage of Th17 cells in lupus subjects with high IFN-α bioactivity (1.9 ± 1.0) compared to lupus subjects with low IFN-α bioactivity (1.2 ± 0.9). Lupus subjects with high IFN-α bioactivity and Th17 cells had significantly higher disease activity (P = 0.04) and serum IL-6 levels (P = 0.01) compared to patients with low IFN-α activity and low Th17 cells.

Type I interferon and Th17 pathways co-exist and co-regulate the pathogenic processes in SLE. Additionally, these studies clearly identify IL-6 as a common link between IFN-I and Th17 pathways in SLE pathogenesis.