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Involvement of interleukin‐21 in the pathophysiology of aplastic anemia
Author(s) -
Zhang Jizhou,
Wu Qingqing,
Shi Jun,
Ge Meili,
Li Xingxin,
Shao Yingqi,
Yao Jianfeng,
Zheng Yizhou
Publication year - 2015
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12471
Subject(s) - foxp3 , il 2 receptor , aplastic anemia , immunology , immune system , proinflammatory cytokine , cytokine , flow cytometry , interleukin 3 , interleukin , t cell , bone marrow , biology , inflammation
Objective Recently enhanced T‐helper type 17 (Th17) immune responses and deficient CD 4 + CD 25 hi FoxP3 + regulatory T cells (Tregs) have been reported in acquired aplastic anemia ( AA ). Interleukin‐21 ( IL ‐21), a CD 4 + 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.