Identification of early myeloid progenitors as immunosuppressive cells
Identification of early myeloid progenitors as immunosuppressive cells
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DOI：
10.1038/srep23115
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发表时间：
2016-03-16
影响因子：
4.6
通讯作者：
Zhou, Zuping
中科院分区：
文献类型：
--
作者：
Pu, Shiming;Qin, Baoxiong;Zhou, Zuping
越来越多的证据表明，造血干/祖细胞（HSPCs），成熟的免疫细胞的前体，可能发挥直接的作用，在免疫监视。早期髓系祖细胞是HSPCs的主要组成部分，并且由于髓系偏向性造血，它们经常在应激中经历广泛的扩增。然而，早期骨髓祖细胞的确切功能仍不清楚。在这里，我们表明，在肿瘤的发展过程中，小鼠粒细胞/巨噬细胞祖细胞（GMP），但不是共同的髓系祖细胞（CMP）显着扩大的骨髓和血液中的小鼠。有趣的是，从荷瘤动物或幼稚动物新鲜分离的GMP和CMP都能够抑制多克隆刺激和同种异体抗原诱导的T细胞增殖，其中肿瘤宿主衍生的细胞具有升高的活性。引人注目的是，这些早期骨髓祖细胞甚至显示出比经典的骨髓源性抑制细胞强得多的抑制能力。GMP的分析表明，他们表达iNOS，并能分泌高水平的NO。进一步的研究unusing iNOS特异性抑制剂揭示，GMP的免疫抑制，在很大程度上，NO依赖性。GMP还可以有效地诱导调节性T细胞发育。这些研究表明，早期骨髓祖细胞可以作为免疫抑制细胞。这一发现为早期髓系祖细胞的功能多样性和可塑性提供了新的见解。
Growing evidence suggests that hematopoietic stem/progenitor cells (HSPCs), precursors of mature immune cells, may play a direct role in immunosurveillance. Early myeloid progenitors are the major components of HSPCs and they often undergo extensive expansion in stress as a result of myeloid-biased hematopoiesis. Yet, the precise function of early myeloid progenitors remains unclear. Here we show that during tumor progression, mouse granulocyte/macrophage progenitors (GMPs) but not common myeloid progenitors (CMPs) are markedly expanded within the bone marrow and blood of mice. Interestingly, both GMPs and CMPs freshly isolated from either tumor-bearing or naive animals are capable of inhibiting polyclonal stimuli-and alloantigen-induced T cell proliferation, with tumor host-derived cells having elevated activities. Strikingly, these early myeloid progenitor cells even display much stronger suppressive capacity than the classical myeloid-derived suppressive cells. Analysis of GMPs indicates that they express iNOS and can secrete high levels of NO. Further studies unusing iNOS specific inhibitors reveal that the immunosuppression of GMPs is, to a large extent, NO-dependent. GMPs can also efficiently induce regulatory T cell development. These studies demonstrate that early myeloid progenitors can act as immunosuppressive cells. This finding provides novel insights into the functional diversity and plasticity of early myeloid progenitor cells.