<br>小鼠自然杀伤细胞体内发育的四阶段模型,Journal of Hematology & Oncology

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小鼠自然杀伤细胞体内发育的四阶段模型
Journal of Hematology & Oncology ( IF 29.5 ) Pub Date : 2022-03-21 , DOI: 10.1186/s13045-022-01243-1
Shoubao Ma _{1,

2} , Michael A Caligiuri _{1,

2,

3,

4} , Jianhua Yu _{1,

2,

3,

4}

Affiliation

自然杀伤（NK）细胞是介导抗病毒和抗肿瘤免疫的主要先天性淋巴细胞。NK 细胞起源于骨髓（BM）中的造血干细胞，并经历谱系规范和成熟。尽管 NK 细胞对先天免疫和创新癌症疗法的发展很重要，但将 NK 祖细胞（NKP）细胞发育与未成熟 NK （iNK）细胞与成熟 NK （mNK）细胞联系起来的详细步骤尚不明确。在这项研究中，我们发现 CD49b、NK1.1 和 NKp46 是在小鼠 Lin-CD122+ NKP 细胞发育过程中依次获得的。引入 NKp46 使我们能够提出一个四阶段发育模型，其中 CD122+NK1.1-CD49b-NKp46-定义了一个 NKP 群体，CD122+NK1.1-CD49b-NKp46-和CD122+NK1.1-CD49b-/+ NKp46-分别定义了 iNK-a 和 iNK-b 群体，CD122+NK1.1-CD49b-NKp46-定义了一个 mNK 群体。这四种 NK 细胞群根据其细胞表面标志物、转录因子和效应分子的表达而具有表型差异。使用体内分化测定离体和过继转移模型，我们证实 NK 细胞发育遵循我们预测的四阶段模型。综上所述，我们的研究结果建立了两个不同的未成熟 NK 细胞群，并定义了小鼠 NK 细胞发育的模型。

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A four-stage model for murine natural killer cell development in vivo

Natural killer (NK) cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. NK cells arise from hematopoietic stem cells in the bone marrow (BM) and undergo lineage specification and maturation. Despite the importance of NK cells for innate immunity and the development of innovative cancer therapy, the detailed steps linking NK progenitor (NKP) cell development through immature NK (iNK) cells to mature NK (mNK) cells are poorly defined. In this study, we found that CD49b, NK1.1, and NKp46 are sequentially acquired during the development of murine Lin−CD122+ NKP cells. Introducing NKp46 allows us to propose a four-stage developmental model, wherein CD122+NK1.1−CD49b−NKp46− defines an NKP population, CD122+NK1.1−CD49b+NKp46− and CD122+NK1.1+CD49b−/+ NKp46− define iNK-a and iNK-b populations, respectively, and CD122+NK1.1+CD49b+NKp46+ defines an mNK population. These four NK cell populations are phenotypically distinct based on their expression of cell surface markers, transcription factors, and effector molecules. Using a differentiation assay ex vivo and adoptive transfer model in vivo, we confirmed that NK cell development follows our predicted four-stage model. Taken together, our findings establish two distinct populations of immature NK cells and define a model for mouse NK cell development.

更新日期：2022-03-21

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