Pu Shiming, Qin Baoxiong, He Huan, Zhan Jinxi, Wu Qiong, Zhang Xinming, Yang Liu, Qu Chunfeng, Zhou Zuping
School of Life Sciences, Guangxi Normal University, Guilin 541004, China.
Guangxi Universities Key Laboratory of Stem cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China.
Sci Rep. 2016 Mar 16;6:23115. doi: 10.1038/srep23115.
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 naïve 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.
越来越多的证据表明，造血干/祖细胞（HSPCs），即成熟免疫细胞的前体，可能在免疫监视中发挥直接作用。早期髓系祖细胞是HSPCs的主要组成部分，由于髓系偏向性造血，它们在应激状态下常经历广泛扩增。然而，早期髓系祖细胞的确切功能仍不清楚。在此我们表明，在肿瘤进展过程中，小鼠骨髓和血液中的粒细胞/巨噬细胞祖细胞（GMPs）而非普通髓系祖细胞（CMPs）显著扩增。有趣的是，从荷瘤动物或未接触肿瘤的动物中新鲜分离的GMPs和CMPs均能够抑制多克隆刺激和同种异体抗原诱导的T细胞增殖，且肿瘤宿主来源的细胞活性更高。引人注目的是，这些早期髓系祖细胞甚至表现出比经典的髓系来源抑制细胞更强的抑制能力。对GMPs的分析表明，它们表达诱导型一氧化氮合酶（iNOS）并能分泌高水平的一氧化氮（NO）。使用iNOS特异性抑制剂的进一步研究表明，GMPs的免疫抑制作用在很大程度上依赖于NO。GMPs还能有效诱导调节性T细胞的发育。这些研究表明早期髓系祖细胞可作为免疫抑制细胞。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。
