Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
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肝脏驻留 NK 细胞在皮肤接触性炎症中赋予适应性免疫
DOI：
10.1172/jci66381
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发表时间：
2013-04-01
影响因子：
15.9
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
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作者：
Peng, Hui;Jiang, Xiaojun;Tian, Zhigang
肝脏自然杀伤（NK）细胞最近被报道在接触性超敏反应（CHS）模型中具有记忆样特性。然而，这些“记忆”NK细胞的表型和起源不能与其他NK细胞亚群区分开来。在这里，我们定义了肝脏NK细胞亚群的转录、表型和功能特征及其在介导CHS中的作用。肝NK细胞可分为两个不同的亚群：CD49a(+)DX5（-）和CD49a(-)DX5（+）。肝脏CD49a(+)DX5(-) NK细胞与其他NK细胞亚群之间存在显著的转录和表型差异。CD49a(+)DX5(-) NK细胞具有记忆潜能，并在半抗原刺激下产生半抗原特异性CHS反应。重要的是，CD49a(+)DX5(-) NK细胞是肝脏常驻细胞，存在于肝窦血中，而不存在于肝的传入和传出血中。此外，它们似乎起源于肝造血祖细胞/干细胞（HPCs/ hsc），而不是来自骨髓，并保持其表型在稳定状态。我们的肝脏驻留NK细胞的发现为NK细胞获得记忆样特性提供了新的思路。
Liver natural killer (NK) cells were recently reported to possess memory-like properties in contact hypersensitivity (CHS) models. However, the phenotype and origin of these "memory" NK cells cannot be distinguished from other NK cell subpopulations. Here, we define the transcriptional, phenotypic, and functional features of liver NK cell subsets and their roles in mediating CHS. Liver NK cells can be divided into two distinct subsets: CD49a(+)DX5(-) and CD49a(-)DX5(+). Substantial transcriptional and phenotypic differences existed between liver CD49a(+)DX5(-) NK cells and other NK cell subsets. CD49a(+)DX5(-) NK cells possessed memory potential and conferred hapten-specific CHS responses upon hapten challenge. Importantly, CD49a(+)DX5(-) NK cells were liver resident and were present in the liver sinusoidal blood, but not the afferent and efferent blood of the liver. Moreover, they appeared to originate from hepatic hematopoietic progenitor/stem cells (HPCs/HSCs) but not from the bone marrow, and maintained their phenotypes in the steady state. Our findings of liver-resident NK cells shed new light on the acquisition of memory-like properties of NK cells.