Characteristics of NK cells from leukemic microenvironment in MLL-AF9 induced acute myeloid leukemia
Characteristics of NK cells from leukemic microenvironment in MLL-AF9 induced acute myeloid leukemia
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MLL-AF9诱导的急性髓系白血病白血病微环境中NK细胞的特征。
DOI：
10.1016/j.molimm.2017.11.003
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Zheng, Guoguang
中科院分区：
文献类型：
--
作者：
Yang, Feifei;Wang, Rong;Zheng, Guoguang
NK 细胞是组织微环境中不可或缺的组成部分，在先天免疫和适应性免疫中发挥着重要作用。 NK细胞的激活和功能受到肿瘤微环境的影响。 NK 细胞也是白血病微环境中的重要参与者。然而，它们在白血病微环境中的特征，包括成熟状态、表型、亚群和功能作用，特别是免疫调节潜力，尚未明确。在这里，我们研究了 MLL-AF9 诱导的小鼠急性髓系白血病 (AML) 模型中 NK 细胞的这些特征。在 AML 脾脏中检测到更成熟的 NK 细胞的增加。脾脏AML微环境促进白血病早中期NK细胞活化。活化的 NK 细胞中细胞毒性分子和细胞因子上调。此外，来自AML微环境的NK细胞不仅通过维持CD4(+)的激活和促进细胞毒性CDS+ T细胞的脱颗粒来调节T细胞功能，而且还通过影响CD4(+) T细胞的分化来调节T细胞功能。此外，DNAM-1（CD226）标记的两个 NK 细胞亚群具有不同的细胞因子表达模式，但对 T 细胞的调节作用相似。总的来说，这些发现强调了 NK 细胞免疫调节作用的重要性，并表明通过操纵 NK 细胞免疫调节活性来治疗白血病的新潜力。
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironrnent, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model. Increase of more mature NK cells were detected in the AML spleen. Splenic AML microenvironment promoted NK cell activation in early and middle stages of leukemia. Cytotoxicity molecules and cytokines were up-regulated in activated NK cells. Furthermore, NK cells from AML micro environment regulated T cell function, not only by maintaining the activation of CD4(+) and promoting the degranulation of cytotoxic CDS+ T cells but also by influencing the differentiation of CD4(+) T cells. Moreover, two NK cell subpopulations marked by DNAM-1 (CD226) had distinct cytokine expression patterns but similar regulatory effects on T cells. Collectively, these findings highlight the significance of immunoregulatory role of NK cells, and suggest novel therapeutic potential for leukemia by manipulating NK cell immunoregulatory activity.