Inscribing the core memories of killers.
Inscribing the core memories of killers.
复制标题
铭刻杀手的核心记忆。
DOI：
10.1038/s41423-018-0178-9
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发表时间：
2019
影响因子：
24.1
通讯作者：
Zajac,AllanJ
中科院分区：
文献类型：
--
作者：
Dulson,SarahJ;Harrington,LaurieE;Zajac,AllanJ
最近对自然杀伤（NK）细胞的研究挑战了免疫记忆是一种仅限于适应性免疫系统的现象的教条。NK细胞受体Ly 49 H和鼠巨细胞病毒（MCMV）编码的糖蛋白m157之间的特异性相互作用导致Ly 49 H + NK细胞亚群的选择性扩增和长寿命记忆样群体的建立。1-3此外，记忆NK细胞显示增强的IFNγ应答，并且将记忆群体转移到幼稚小鼠中赋予增强的针对感染诱导的死亡率的保护。这些观察结果沿着与CD 8 T细胞重叠的细胞毒性和细胞因子分泌功能，导致将NK细胞描述为先天性和适应性免疫系统之间的桥梁。尽管NK和CD 8 T细胞反应具有共同的特征，但它们的特异性、动力学、活化和功效之间存在重要区别。此外，虽然幼稚、效应和记忆CD 8 T细胞的染色质景观越来越明确，但对NK细胞获得记忆特性时发生的基因可及性变化知之甚少。Lau等人最近的一份报告揭示了与记忆NK细胞形成相关的关键表观遗传变化，并为识别记忆NK和T细胞共享的核心表观遗传特征奠定了基础。6为了了解基因可及性和表达的变化，这些变化发生在初始NK细胞被激活、产生效应子能力并最终转变为记忆时，Lau等人使用高通量测序（ATAC-seq）与RNA-seq对在MCMV应答期间不同时间点获得的脾Ly 49 H + NK细胞进行了转座酶可及染色质测定。分析揭示了基因可及性的短暂和长期变化。毫不奇怪，NK细胞中的大部分表观遗传重塑发生在感染后的前几天，并且通常与转录活性的变化相匹配。在此形成阶段，染色质结构的这些早期修饰不仅允许产生NK细胞介导的MCMV清除所必需的效应分子，而且随着细胞克隆扩增和分化，开始印记记忆性状（图1）。
Recent studies on natural killer (NK) cells have challenged the dogma that immunological memory is a phenomenon restricted to the adaptive immune system. Specific interactions between the NK cell receptor Ly49H and the murine cytomegalovirus virus (MCMV)-encoded glycoprotein m157 result in selective expansion of the Ly49H+ NK cell subpopulation and the establishment of a long-lived memory-like population. 1–3 Further, memory NK cells show augmented IFNγ responses, and transfer of the memory population into naive mice confers enhanced protection against infection-induced mortality. 1 These observations along with cytotoxicity and cytokine secretion functions that overlap with CD8 T cells have led to the description of NK cells as a bridge between the innate and adaptive immune systems. 4 Despite their common features, important distinctions exist between the specificity, kinetics, activation, and efficacy of NK and CD8 T cell responses. Furthermore, while the chromatin landscape of naive, effector, and memory CD8 T cells is increasingly well defined, 5 less is known about changes in gene accessibility that occur as NK cells gain memory properties. A recent report by Lau et al. uncovers key epigenetic changes that are associated with the formation of memory NK cells and lays the foundation for the identification of a core epigenetic signature shared by memory NK and T cells. 6To understand the changes in gene accessibility and expression that occur as naive NK cells become activated, develop effector capabilities, and ultimately transition into memory, Lau et al. performed the assay for transposase-accessible chromatin using high-throughput sequencing (ATAC-seq) in parallel with RNA-seq on splenic Ly49H+ NK cells procured at distinct time points during the response to MCMV. The analysis reveals both transient and long-lasting changes in gene accessibility. Not surprisingly, the bulk of the epigenetic remodeling in NK cells occurs during the first several days following infection and generally matches changes in transcriptional activity. These early modifications in chromatin architecture during this formative phase not only permit the production of effector molecules necessary for the NK cell-mediated clearance of MCMV, but also begin to imprint memory traits as the cells clonally expand and differentiate (Fig. 1).