The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis.

T helper type 17 (Th17) cells, a novel distinct subset of Th cell, can secrete interleukin (IL)-17 in humans. Although recent data suggest that Th17 cells and IL-17 play an important role in the pathogenesis of lupus nephritis (LN), the expression of Th17-related cytokines in the kidneys of SLE patients has not been studied in detail. In the present study, we investigated circulating Th17-cell frequencies using flow cytometry and serum Th17-related cytokine levels by enzyme-linked immunosorbent assay (ELISA) in 24 LN patients (17 patients with class IV and seven patients with class V) and 12 healthy controls. We also investigated glomerular Th17-related cytokine expression in LN patients and minimal change nephropathy (MCN) patients using immunohistochemistry. Our results showed significantly higher median frequencies of circulating Th17 cells in LN patients (0.68%) than in healthy controls (0.12%, p < 0.001). Serum levels of IL-17, IL-6 and IL-23 were significantly higher in LN patients (median 7.26, 232.60 and 37.01 pg/ml, respectively) than in healthy controls (median 0.82, 34.60 and 7.42 pg/ml, respectively; all p < 0.001). Circulating Th17-cell frequencies were positively correlated with SLEDAI, renal SLEDAI and histological activity index, the degree of cellular crescent and endocapillary proliferation. Significantly higher levels of glomerular IL-17 and IL-23 expression were observed in renal biopsies from class IV LN patients as compared to those from MCN patients and normal controls. Glomerular IL-17 and IL-23 expression levels were positively correlated with renal SLEDAI and histological activity index for LN patients. Our results suggest the potential role of the IL-23/Th17 axis in the intra-renal inflammation of SLE.