Background Systemic lupus erythematosus (SLE) is an autoimmune disease in which various organs and tissues are damaged through abnormal immune responses mediated by tissue-binding autoantibodies. Though, the exact pathogenic mechanism is not clearly elucidated, estrogens are thought to play an important role because over 90% of SLE patients are women. IL-21 is an important cytokine which is produced by T cells, especially Th17 and induces B cell activation. Thus, it has been suggested that IL-21 plays a critical role in the pathogenesis of autoimmune diseases.
Objectives We investigated the effect of estrogens on the production of IL-21 and subsequent B cell activation in SLE patients.
Methods Peripheral blood mononuclear cells (PBMCs) were obtained from peripheral blood of SLE patients and healthy controls. CD4+ T cells, non CD4+ T cells, B cells were isolated using micro beads. The expression of IL-21 and its receptors was assessed by ELISA (serum) and real time PCR (PBMCs, CD4+ cells). The level of immunoglobulin G secreted by activated B cells were measured with specific ELISA.
Results The expression of IL-21 and its receptors in serum, PBMC, and CD4+ T cells was higher in patients with SLE compared to healthy controls. The production of IL-21 was increased when the cells are stimulated with estrogen in dose- and time- dependent manners. IL-21 production was decreased in the presence of MAP kinase (MEK, p38, JNK) inhibitors. B cells of healthy controls showed an increased antibody production when they were co-cultured with estrogen-stimulated CD4+ T cells of patients with SLE. IL-21 antibodies suppressed the increased antibody production of the co-culture systems.
Conclusions This study revealed a possible role of estrogens in the pathogenesis of SLE. Estrogens increase the production of IL-21 by activating CD4+ T cells via MAP kinase dependent pathways in SLE patients.
Disclosure of Interest None Declared
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