Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, Jinan, 250012, China.
Stem Cell Rev Rep. 2017 Dec;13(6):705-712. doi: 10.1007/s12015-017-9761-1.
The replenishment of all blood cell lineages is hierarchically organized by the process of hematopoiesis, which is based on the differentiation pathways of hematopoietic stem and progenitor cells (HSPCs). Due to the ability to balance between self-renewal and differentiation, hematopoietic stem cells (HSCs) can generate the appropriate cell type that is required by the immune system and peripheral blood in response to physiological or pathological conditions. Numerous studies have shown that some proinflammatory cytokines contribute to the regulation of the various hematopoietic compartments. Of these, IFN-γ is a type II interferon primarily produced by T cells and natural killer cells, and plays a major role in the defense against invading pathogens and transformed cancer cells; moreover, a growing amount of research indicates that it exerts negative or positive regulatory effect on hematopoiesis. Although IFN-γ is a widely regarded negative regulator of HSC proliferation, it also participates in some chronic infections or hematological malignancies that induce bone marrow failure. Recent studies have demonstrated unexpected effects of IFN-γ, including the promotion of HSC formation and the stimulation of myelopoiesis. Here, we review the direct and indirect effects of IFN-γ on hematopoiesis, as well as the underlying signaling mechanisms of how IFN-γ modulates the self-renewal, cell cycle entry, and proliferation of HSCs. Next, we describe how IFN-γ affects different stages of the lineage differentiation from HSCs. Finally, we discuss the relationship between IFN-γ and compensatory extramedullary hematopoiesis, as well as some related clinical diseases.
所有血细胞谱系的补充都是由造血过程按层次组织的，造血过程基于造血干细胞和祖细胞（HSPCs）的分化途径。由于具有自我更新和分化之间的平衡能力，造血干细胞（HSCs）可以在响应生理或病理条件时生成免疫系统和外周血所需的适当细胞类型。许多研究表明，一些促炎细胞因子有助于调节各种造血区室。在这些细胞因子中，IFN-γ是一种主要由 T 细胞和自然杀伤细胞产生的 II 型干扰素，在抵御入侵病原体和转化癌细胞方面发挥着重要作用；此外，越来越多的研究表明，它对造血具有负或正调节作用。尽管 IFN-γ被广泛认为是 HSC 增殖的负调节剂，但它也参与了一些导致骨髓衰竭的慢性感染或血液恶性肿瘤。最近的研究表明 IFN-γ具有意想不到的作用，包括促进 HSC 形成和刺激髓样造血。在这里，我们综述了 IFN-γ对造血的直接和间接影响，以及 IFN-γ调节 HSCs 自我更新、细胞周期进入和增殖的信号转导机制。接下来，我们描述了 IFN-γ如何影响 HSCs 向不同谱系分化的各个阶段。最后，我们讨论了 IFN-γ与代偿性骨髓外造血之间的关系，以及一些相关的临床疾病。
