Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells.
Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells.
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DOI：
10.18632/oncotarget.16377
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发表时间：
2017-05-02
期刊：
影响因子：
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通讯作者：
Patra AK
中科院分区：
文献类型：
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作者：
Giampaolo S;Wójcik G;Serfling E;Patra AK
IL-2在HSC维持中的作用尚不清楚。在这里，我们发现IL 2 −/−小鼠在HSC维持方面出现严重异常，导致造血缺陷。然而，缺乏IL-2信号传导对淋巴细胞和红细胞生成有害，IL 2 −/−小鼠的骨髓生成增强。对IL-2 −/−小鼠中造血失调的潜在机制的研究表明，IL-2-Treg细胞轴对于HSC维持和正常造血是不可或缺的。缺乏Treg活性导致IFN-？通过活化的T细胞的产生和骨髓（BM）中HSC的扩增。然而，恢复Treg群体成功地挽救了IL 2 −/−小鼠中的HSC维持，阻止了IFN-？即使在没有Treg细胞的情况下，活性也可以做同样的事情。我们的研究表明，IL-2和IFN-？活性是至关重要的稳态造血，并在临床条件下的骨髓衰竭，IL-2或抗IFN-？治疗可能有助于恢复造血。
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2−/− mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2−/− mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2−/− mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-? production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2−/− mice, preventing IFN-? activity could do the same even in the absence of Treg cells. Our study suggests that equilibrium in IL-2 and IFN-? activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-? treatment might help to restore hematopoiesis.