Above all, IL-21 promotes the differentiation of B cells into plasma cells and plays a critical role in regulating immunoglobulin production.57,58 Plasma levels of IL-21 are significantly elevated in SLE patients compared with those in healthy controls, and high concentrations of IL-21 are associated with disease severity and SLEDAI scores.59 In this study, we observed significantly decreased CD40L, ICOS, and IL-21 expression in SLE CD4+ T cells after BCL-6 expression was knocked down. Here, ICOS is linked to systemic lupus erythematosus.