Mesenchymal stromal cells of the bone marrow and natural killer cells: cell interactions and cross modulation
Mesenchymal stromal cells of the bone marrow and natural killer cells: cell interactions and cross modulation
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DOI：
10.1007/s12079-018-0448-4
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发表时间：
2018-12-01
影响因子：
4.1
通讯作者：
Lagneaux, Laurence
中科院分区：
文献类型：
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作者：
Najar, Mehdi;Fayyad-Kazan, Mohammad;Lagneaux, Laurence
骨髓间充质干细胞 (BM-MSC) 是多能祖细胞，已显示出在多种不同治疗应用中的前景。由于它们能够调节多种类型免疫细胞的功能，因此 BM-MSC 在细胞免疫治疗领域非常重要。了解 BM-MSC-自然杀伤 (NK) 细胞相互作用对于提高其治疗效率至关重要。在这里，我们观察到 NK 细胞激活细胞因子（例如 IL-2、IL-12、IL-15 和 IL-21）的类型强烈影响它们与 BM-MSC 相互作用的结果。共培养后，介导 BM-MSC 和 NK 细胞之间串扰的配体（CD112、CD155、ULPB-3）和受体（LAIR、NCR）的表达模式受到严格调节。 BM-MSC 部分损害 NK 细胞增殖，但上调其 IFN- 和 TNF- 的分泌。由于它们具有细胞毒性，活化的 NK 细胞会诱导 BM-MSC 的杀伤。事实上，BM-MSC 引发了 NK 细胞的脱颗粒并增加了穿孔素和颗粒酶的释放。有趣的是，活化的 NK 细胞诱导 BM-MSC 内产生 ROS，导致其活力下降并减少丝氨酸蛋白酶抑制剂 B9 的表达。总的来说，我们的观察表明 BM-MSC-NK 细胞相互作用可能会影响两种细胞类型的免疫生物学。一旦这些问题得到充分表征，BM-MSC 的治疗潜力将显着提高。
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent progenitor cells that have shown promise for several different therapeutic applications. As they are able to modulate the function of several types of immune cells, BM-MSCs are highly important in the field of cell-based immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is crucial for improving their therapeutic efficiency. Here, we observed that the type of NK cell-activating cytokine (e.g., IL-2, IL-12, IL-15 and IL-21) strongly influenced the outcomes of their interactions with BM-MSCs. The expression patterns of the ligands (CD112, CD155, ULPB-3) and receptors (LAIR, NCR) mediating the cross-talk between BM-MSCs and NK cells were critically modulated following co-culture. BM-MSCs partially impaired NK cell proliferation but up-regulated their secretion of IFN- and TNF-. As they are cytotoxic, activated NK cells induced the killing of BM-MSCs. Indeed, BM-MSCs triggered the degranulation of NK cells and increased their release of perforin and granzymes. Interestingly, activated NK cells induced ROS generation within BM-MSCs that caused their decreased viability and reduced expression of serpin B9. Collectively, our observations reveal that BM-MSC-NK cell interactions may impact the immunobiology of both cell types. The therapeutic potential of BM-MSCs will be significantly improved once these issues are well characterized.