Involvement of interleukin-21 in the pathophysiology of aplastic anemia
Involvement of interleukin-21 in the pathophysiology of aplastic anemia
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IL-21 参与再生障碍性贫血的病理生理学
DOI：
10.1111/ejh.12471
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发表时间：
2015-07-01
影响因子：
3.1
通讯作者：
Zheng, Yizhou
中科院分区：
文献类型：
--
作者：
Zhang, Jizhou;Wu, Qingqing;Zheng, Yizhou
目的近期报道了获得性再生障碍性贫血（AA）中T辅助型17 （Th17）免疫应答增强和CD4(+)CD25(hi)FoxP3（+）调节性T细胞（Tregs）缺陷。白细胞介素-21 （IL-21）是一种CD4(+) t细胞衍生的促炎细胞因子，可调节Th17细胞和Tregs之间的平衡。然而，它在AA中的作用仍不清楚。方法采用实时荧光定量PCR法检测il -21基因的表达。ELISA法检测血浆和细胞培养上清中的细胞因子。流式细胞术检测产生细胞因子的T细胞和treg细胞。结果新诊断AA患者外周血CD4(+) T细胞IL-21 mRNA水平及血浆IL-21水平均显著升高。此外，il -21生成CD4(+) T细胞的升高伴随着Th17细胞的积累和Tregs的降低，并与AA活性相关。在体外实验中，IL-21不仅抑制FoxP3的表达，还能诱导AA患者CD4(+) T细胞中IL-17的表达。更重要的是，我们发现AA患者骨髓内的T细胞（BM）处于升高的激活状态，这可能与IL-21有关。结论IL-21通过促进Th17细胞、激活BM T细胞和抑制Tregs，在AA免疫稳态的破坏中起关键作用。
ObjectiveRecently enhanced T-helper type 17 (Th17) immune responses and deficient CD4(+)CD25(hi)FoxP3(+) 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.MethodsIL-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.ResultsIL-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.ConclusionOur 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.