Expression, source and significance of interleukin-21 in patients with systemic lupus erythematosus and its correlation with interleukin-17

Objective The expression and significance of interleukin (IL) -21 in patients with systemic lupus erythematosus (SLE) was studied and its correlation with IL-17 was explored. Methods Peripheral blood mononuclear cells(PBMCs) and serum were obtained from 36 patients with newly-onset SLE and 28 healthy controls. The frequency of CD4 + T cells producing IL-21 and IL-17 were measured by flow cytometry. The expression of IL-21-associated transcriptor signal transducer and activator of transcription 3, signal transducer and activator of transcription 3 (STAT3) mRNA was quantitatively measured by real-time polymerase chain reaction (RT-PCR). The level of IL-21 in serum was detected by enzyme linked immunosorbent assay (ELISA) before and after 1 month treatment. CD4+ cells from SLE patients were sorted by microbeads, and CD4+CD25+ cells were sorted by flow cytometry, the frequency of CD4+IL-21+ T, IL-21+ Th1, IL-21+ Th2, IL-21+ Th17, IL-21+ Treg and IL-21+ Tfh-like cells in peripheral blood were detected by flow cytometry; T- test and Pearson correlation analysis were used for statistical analysis. Results ① The percentages of IL-21+ CD4+ T cells in PBMCs were significantly higher in SLE patients [(10.0±5.9)%] than healthy controls [(4.4±1.8)%] (t= 4.87, P<0.01), and IL-21 expression in severe SLE patients [(14.3±5.4)%] was significantly higher than that in mild SLE patients [(6.4±2.9)%] (t=4.90, P<0.01); ② Serum level of IL-21 in SLE patients [(317±27) pg/ml] was also significantly higher than human controls [(111 ± 12) pg/ml] (t=5.60, P<0.01), and dropped rapidly after treatment [(266 ± 35) pg/ml] (t=11.6, P<0.01). ③ The mRNA expression of STAT3 was significantly higher in SLE patients (0.52±0.25) compared with HC (0.32±0.12) (t=2.39, P<0.05). ④ IL-21 was produced broadly by Th1, Th2, Th17, Tfh and Treg cells in SLE patients. ⑤ The expression of IL-21 on CD4+ T cells was positively correlated with SLEDAI (r=0.634, P<0.01), serum IgG (r=0.585, P<0.01), and titters of anti-dsDNA (r=0.408, P< 0.05), but negatively correlated with complement 3 (r=-0.554, P<0.05). ⑥ The percentages of IL-17+ CD4+ T cells in PBMC and the level of IL-21 in serum were significantly higher in SLE patients than healthy controls [(1.7±0.7)% vs (1.0±0.5)%, t=3.04, P=0.006; (62±26) pg/ml vs (41±15) pg/ml, t=2.92, P=0.015], IL-17 on CD4+ T cells was positively correlated with IL-21 on CD4+ T cells (r=0.488, P=0.029). Conclusion Elevated IL-21 is closely related to disease activity in SLE and produced broadly by Th1, Th2, Th17, Tfh and Treg cells, suggesting that IL-21 may be involved in the pathogenesis of SLE and when combined with IL-17 together will induce the onset of SLE. Key words: Lupus erythematosus, systemic; Interleukin-21; Interleukin-17; T-lymphocytes, helper-inducer