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

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-γt) 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.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-γt 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.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.Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. The presence of antibodies against dsDNA is a hallmark of SLE. Although the precise pathogenesis of SLE has not been fully elucidated, disturbances in T-cell and B-cell homeostasis appear to contribute to the inflammatory pathology of SLE. Several cytokines have been demonstrated to be crucial for the regulation of B- and T-cell homeostasis. Recently, the novel cytokine interleukin (IL)-21 has been found to play a pivotal role in differentiation and function of T-cells. In particular, IL-21 drives an inflammatory T-cell response by triggering the production of IL-17, which is thought to be a crucial cytokine for inflammatory processes as occur in lupus nephritis in SLE [1].The novel class I cytokine IL-21 is