Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients. Methods: Peripheral blood of 34 SLE patients and 18 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore (Ca-Io). Percentages of IL-21-and IL-17A expressing T-cells were analysed by flow cytometry. The expression levels of the transcription factors B-cell lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-gamma t) were assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21 receptor (IL-21R) expression on B-and T-cells of patients and HC was analyzed. Results: Significantly increased percentages of IL-21 expressing CD4(+) T-cells and CD8(+) T-cells were found in SLE patients as compared to HC. The percentages of IL-21(+) CD4(+) T-cells and CD8(+) T-cells correlated significantly with the percentages of IL-17A(+) CD4(+) T-cells and CD8(+) T-cells, respectively. The relative expression of BCL-6 and ROR-gamma t did not differ between SLE patients and HC. IL-21R expression occurred mainly on B-cells and was not different comparing SLE patients and HC. Conclusions: This study demonstrates an increased proportion of IL-21(+) T-cells in SLE patients correlating with the proportion of IL-17(+) T-cells. This suggests a pivotal role of IL-21 in the pathogenesis of SLE.