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

Dolff, Sebastian LSF; Abdulahad, Wayel H.; Westra, Johanna; Doornbos-van der Meer, Berber; Limburg, Pieter C.; Kallenberg, Cees G.M.; Bijl, Marc

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-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.
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-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.
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.

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Dolff, Sebastian / Abdulahad, Wayel H. / Westra, Johanna / et al: Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus. 2018.

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