Interferon-γ exerts dual functions on human erythropoiesis via interferon regulatory factor 1 signal pathway
Interferon-γ exerts dual functions on human erythropoiesis via interferon regulatory factor 1 signal pathway
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干扰素-γ 通过干扰素调节因子 1 信号通路对人类红细胞生成发挥双重功能
DOI：
10.1016/j.bbrc.2019.10.068
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发表时间：
2020
影响因子：
3.1
通讯作者：
Lei Zhang
中科院分区：
文献类型：
--
作者：
Wentian Wang;Huijuan Zhao;Yang Yang;Ying Chi;Xiang Lv;Lei Zhang
摘要造血功能受微环境因素的系统调控。积极和消极的因素协调在一起，形成了一个复杂的血液系统。干扰素-γ(干扰素-γ)是再生障碍性贫血等多种造血功能异常的常见病因。然而，它对单系发育的影响，特别是对红细胞生成的影响，还没有从细胞的角度完全阐明。在本研究中，我们研究了干扰素γ的行为，发现干扰素γ在红细胞生成中具有双重功能，它不仅阻断了红系的承诺，而且加速了红系的分化过程，最终导致了红系窗口的清除。干扰素γ甚至可以在没有促红细胞生成素(EPO)存在的情况下强烈地启动早期分化。干扰素调节因子1被确认为重要的下游效应因子，其异位过表达也可起到与干扰素γ相同的作用。这些结果表明，干扰素γ-IRF1轴在红细胞生成中起双向作用，阻碍了获得红系血统的途径，并将即将到来的细胞推向分化终点。该模型为进一步了解干扰素γ-IRF1轴在正常造血和异常血液病，尤其是再生障碍性贫血中的作用机制提供了新的思路。
AbstractsHematopoiesis is systematically regulated by microenvironmental factors. The positive and negative factors coordinated together to yield a complicated blood system. Interferon-γ (IFNγ) has been identified as a common cause of various hematopoietic abnormalities, such as aplastic anemia. However, its impact on monolineage development, especially erythropoiesis, has not been fully elucidated from the cellular angle. In this study, we investigated the behavior of IFNγ and found that IFNγ plays dual functions on erythropoiesis; it not only blocks the erythroid lineage commitment but also accelerates the erythroid differentiation process, ultimately leading to the erythropoietic window clearance. IFNγ can even powerfully initiate early differentiation without the existence of erythropoietin (EPO). Interferon regulatory factor 1 (IRF1) was confirmed as the essential downstream effector, and its ectopic overexpression can also have the same effect as that of IFNγ. These results reveal that the IFNγ–IRF1axis plays a bidirectional role on erythropoiesis, impeding the access to erythroid lineage and driving the coming cells toward the differentiation endpoint. This model may place an innovative implication for IFNγ–IRF1axis to understand its in-depth mechanism on normal hematopoiesis and abnormal blood disorders, especially aplastic anemia.