Objective
Recently enhanced T‐helper type 17 (Th17) immune responses and deficient CD4+CD25hiFoxP3+ regulatory T cells (Tregs) have been reported in acquired aplastic anemia (AA). Interleukin‐21 (IL‐21), a CD4+ T‐cell‐derived proinflammatory cytokine, modulates the balance between Th17 cells and Tregs. However, its role in AA remains unclear.
Methods
IL‐21 gene expression was examined by quantitative real‐time PCR. Cytokines in plasma and cell culture supernatants were detected by ELISA. Cytokines‐producing T cells and Tregs were evaluated by flow cytometry.
Results
IL‐21 mRNA levels in circulating CD4+ T cells and IL‐21 levels in blood plasma were markedly increased in patients with newly diagnosed AA. Moreover, elevated IL‐21‐producing CD4+ T cells were accompanied by Th17 cells accumulation and Tregs decrease, and correlated with AA activity. In vitro, IL‐21 not only inhibited the expression of FoxP3, but also induced the expression of IL‐17 in CD4+ T cells of AA patients. More importantly, we found that T cells within the bone marrow (BM) of AA patients were in a heightened activation state, which may be related to IL‐21.
Conclusion
Our data suggested a critical role of IL‐21 in breaking immune homeostasis in AA by promoting Th17 cells, activating BM T cells and suppressing Tregs.