Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China.
Beijing Engineering Laboratory for Cellular Therapy, Beijing, China.
Front Immunol. 2021 Mar 18;12:610789. doi: 10.3389/fimmu.2021.610789. eCollection 2021.
Natural killer (NK) cells are lymphocytes primarily involved in innate immunity and possess important functional properties in anti-viral and anti-tumor responses; thus, these cells have broad potential for clinical utilization. NK cells originate from hematopoietic stem cells (HSCs) through the following two independent and continuous processes: early commitment from HSCs to IL-15-responsive NK cell progenitors (NKPs) and subsequent differentiation into mature NK cells in response to IL-15. IL-15 is the most important cytokine for NK cell development, is produced by both hematopoietic and nonhematopoietic cells, and functions through a distinct delivery process termed transpresentation. Upon being transpresented to NK cells, IL-15 contributes to NK cell development the activation of several downstream signaling pathways, including the Ras-MEK-MAPK, JAK-STAT5, and PI3K-ATK-mTOR pathways. Nonetheless, the exact role of IL-15 in NK cell development has not been discussed in a consecutive and comprehensive manner. Here, we review current knowledge about the indispensable role of IL-15 in NK cell development and address which cells produce IL-15 to support NK cell development and when IL-15 exerts its function during multiple developmental stages. Specifically, we highlight how IL-15 supports NK cell development by elucidating the distinct transpresentation of IL-15 to NK cells and revealing the downstream target of IL-15 signaling during NK cell development.
自然杀伤 (NK) 细胞是主要参与固有免疫的淋巴细胞，在抗病毒和抗肿瘤反应中具有重要的功能特性；因此，这些细胞具有广泛的临床应用潜力。NK 细胞由造血干细胞 (HSCs) 通过以下两个独立且连续的过程产生：HSCs 早期向白细胞介素 15 反应性 NK 细胞前体 (NKP) 的定向，以及随后在白细胞介素 15 的作用下分化为成熟 NK 细胞。白细胞介素 15 是 NK 细胞发育最重要的细胞因子，由造血细胞和非造血细胞产生，并通过一种称为转呈的独特传递过程发挥作用。白细胞介素 15 转呈到 NK 细胞后，有助于 NK 细胞的发育和几个下游信号通路的激活，包括 Ras-MEK-MAPK、JAK-STAT5 和 PI3K-ATK-mTOR 通路。然而，白细胞介素 15 在 NK 细胞发育中的确切作用尚未以连续和全面的方式进行讨论。在这里，我们回顾了关于白细胞介素 15 在 NK 细胞发育中不可或缺作用的现有知识，并讨论了哪些细胞产生白细胞介素 15 以支持 NK 细胞发育，以及白细胞介素 15 在 NK 细胞发育的多个阶段何时发挥作用。具体而言，我们通过阐明白细胞介素 15 向 NK 细胞的独特转呈以及揭示 NK 细胞发育过程中白细胞介素 15 信号的下游靶标，强调了白细胞介素 15 如何支持 NK 细胞的发育。
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