NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production
NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production
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DOI：
10.1038/s41423-019-0277-2
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发表时间：
2020-04-01
影响因子：
24.1
通讯作者：
Watzl, Carsten
中科院分区：
文献类型：
--
作者：
Anft, Moritz;Netter, Petra;Watzl, Carsten
自然杀伤(NK)细胞参与机体对病原体和肿瘤的早期免疫防御，发挥免疫效应和调节细胞的重要作用。NK细胞介导的对感染或癌细胞的清除是一个高度调控的过程，需要细胞接触的形成，免疫突触的建立，以及溶解颗粒的极化和释放。此外，NK细胞与靶细胞的分离对于NK细胞在称为连续杀伤的过程中结合和杀死其他细胞是重要的。然而，人们对这种脱离过程知之甚少。在这里，我们表明，NK细胞的脱离与靶细胞的成功杀伤直接相关。由于NK细胞毒性降低或靶细胞抵抗力增加而导致的杀伤抑制会导致缺陷的脱离和接触时间的延长。这种作用导致NK细胞持续的钙离子流动和促炎细胞因子的高分泌。通过减少脱落将细胞毒性缺陷与细胞因子分泌增加联系在一起，可以解释几种疾病的炎性病理。
Natural killer (NK) cells participate in early immune defenses against pathogens and tumors and play a major role as immune effector and regulatory cells. The NK cell-mediated elimination of an infected or cancerous cell is a highly regulated process that requires the formation of a cell contact, the establishment of an immunological synapse and the polarization and release of lytic granules. Additionally, the detachment of NK cells from target cells is important for NK cells to bind and kill other cells in a process called serial killing. However, very little is known about this detachment process. Here, we show that NK detachment is directly connected to the successful killing of a target cell. The inhibition of killing due to reduced NK cell cytotoxicity or increased target cell resistance results in defective detachment and prolonged contact times. This effect leads to sustained Ca2+ flux in NK cells and the hypersecretion of proinflammatory cytokines. Linking defective cytotoxicity with enhanced cytokine secretion via reduced detachment may explain inflammatory pathologies in several diseases.