The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.
The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.
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DOI：
10.3389/fcell.2021.609532
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发表时间：
2021
影响因子：
5.5
通讯作者：
Barda-Saad M
中科院分区：
文献类型：
--
作者：
Ben-Shmuel A;Sabag B;Biber G;Barda-Saad M
自然杀伤（NK）细胞是先天性淋巴细胞，在清除病毒感染和恶性细胞中发挥关键作用。来自NK表面受体的激活和抑制信号之间的平衡支配NK细胞免疫应答。细胞骨架促进大多数NK细胞效应子功能，如运动性、浸润、与靶细胞的缀合、免疫突触组装和细胞毒性。虽然许多研究已经表征了促进免疫细胞中肌动蛋白重组的信号通路，但尚不完全清楚免疫突触处的特定细胞骨架结构如何促进效应器功能，以及细胞骨架动力学如何影响下游信号通路和激活。此外，采用先进的成像技术的开创性研究才刚刚开始揭示的结构复杂性决定NK细胞的激活阈值，它是越来越清楚，一个独特的组织的细胞骨架和信号受体在NK免疫突触起着决定性的作用，在激活和耐受。在这里，我们审查的作用，肌动蛋白细胞骨架在NK细胞。我们专注于肌动蛋白动力学如何影响溶细胞颗粒的分泌，NK细胞的运动，和NK细胞浸润通过组织进入炎症部位。我们还将描述额外的细胞骨架成分，非肌肉肌球蛋白II和微管在NK细胞活性中发挥关键作用。此外，将特别强调细胞骨架在免疫突触组装中的作用，以及细胞骨架辅助蛋白的突变或下调如何影响健康和疾病中的NK细胞功能。
Natural killer (NK) cells are innate lymphoid cells, which play key roles in elimination of virally infected and malignant cells. The balance between activating and inhibitory signals derived from NK surface receptors govern the NK cell immune response. The cytoskeleton facilitates most NK cell effector functions, such as motility, infiltration, conjugation with target cells, immunological synapse assembly, and cytotoxicity. Though many studies have characterized signaling pathways that promote actin reorganization in immune cells, it is not completely clear how particular cytoskeletal architectures at the immunological synapse promote effector functions, and how cytoskeletal dynamics impact downstream signaling pathways and activation. Moreover, pioneering studies employing advanced imaging techniques have only begun to uncover the architectural complexity dictating the NK cell activation threshold; it is becoming clear that a distinct organization of the cytoskeleton and signaling receptors at the NK immunological synapse plays a decisive role in activation and tolerance. Here, we review the roles of the actin cytoskeleton in NK cells. We focus on how actin dynamics impact cytolytic granule secretion, NK cell motility, and NK cell infiltration through tissues into inflammatory sites. We will also describe the additional cytoskeletal components, non-muscle Myosin II and microtubules that play pivotal roles in NK cell activity. Furthermore, special emphasis will be placed on the role of the cytoskeleton in assembly of immunological synapses, and how mutations or downregulation of cytoskeletal accessory proteins impact NK cell function in health and disease.
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DOI：
10.1083/jcb.201201018
发表时间：
2012-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Babich A;Li S;O'Connor RS;Milone MC;Freedman BD;Burkhardt JK
通讯作者：
Burkhardt JK
影响因子：
7.3
作者：
Bálint Š;Lopes FB;Davis DM
通讯作者：
Davis DM
影响因子：
15.3
作者：
ALLAVENA, P;PAGANIN, C;MANTOVANI, A
通讯作者：
MANTOVANI, A
影响因子：
2.2
作者：
Banerjee, Pinaki P.;Orange, Jordan S.
通讯作者：
Orange, Jordan S.
影响因子：
11.4
作者：
Barda-Saad, Mira;Shirasu, Naoto;Samelson, Lawrence E.
通讯作者：
Samelson, Lawrence E.