NKp80 Defines a Critical Step during Human Natural Killer Cell Development.
NKp80 Defines a Critical Step during Human Natural Killer Cell Development.
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DOI：
10.1016/j.celrep.2016.05.095
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发表时间：
2016-07-12
期刊：
影响因子：
8.8
通讯作者：
Caligiuri MA
中科院分区：
文献类型：
--
作者：
Freud AG;Keller KA;Scoville SD;Mundy-Bosse BL;Cheng S;Youssef Y;Hughes T;Zhang X;Mo X;Porcu P;Baiocchi RA;Yu J;Carson WE 3rd;Caligiuri MA
人类自然杀伤细胞（NK）在继发性淋巴组织（slt）中的发育经历了不同的阶段。根据c型凝集素样表面激活受体NKp80的表达，我们鉴定了两个SLT谱系(Lin)−CD34−CD117+/−CD94+CD16−“4期”亚群：NKp80−（“4a”期）和NKp80+（“4b”期）。4b期细胞表达更多的转录因子T-BET和EOMES，产生干扰素γ，并具有细胞毒性，而4a期细胞表达更多的转录因子rorγ γt和AHR，并产生白细胞介素22，类似于SLT Lin - CD34 - CD117+CD94 - CD16 -“3期”细胞，其表型与第3组先天淋巴样细胞（ILC3s）重叠。与树突状细胞共培养或移植到免疫缺陷小鼠体内可产生来自3期和4a期群体的成熟NK细胞。这些数据确定NKp80是slt中NK细胞成熟的标记物，并通过具有ilc3相关特征的4a期中间体支持人类NK细胞发育模型。人类自然杀伤细胞（NK）具有强大的抗癌效应；NK细胞如何在人体中发育尚不清楚。Freud等人证明，NKp80的表达标志着次生淋巴组织中功能成熟的NK细胞的发育。这些发现有助于确定人类NK细胞发育的途径。
Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)−CD34−CD117+/−CD94+CD16− “stage 4” subsets according to expression of the C-type lectin-like surface activating receptor, NKp80: NKp80− (stage “4a”) and NKp80+ (stage “4b”). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin−CD34−CD117+CD94−CD16− “stage 3” cells whose phenotype overlaps with that of Group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features. Human natural killer (NK) cells have potent effector functions against cancer; how NK cells develop in humans is unclear. Freud et al. demonstrate that NKp80 expression marks functionally mature NK cells as they develop in secondary lymphoid tissues. These findings help define the pathway of human NK cell development.