Division of Head and Neck Surgery, Department of Otolaryngology, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Eur J Immunol. 2018 May;48(5):771-776. doi: 10.1002/eji.201747289. Epub 2018 Feb 12.
Human natural killer (NK) cells are divided into two subsets: CD56 and CD56 NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions. We found that AhR mRNA is highly expressed in peripheral CD56 NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56 NK cells were highly sensitive to AhR ligands. Specifically, AhR ligands modulated their activation and their expression of NK cell receptors, as well as cytokine secretion which is the major function of these cells. As CD56 NK cells are highly enriched in tissues and in tumors, our observations point to a possible effect of local AhR ligands in the regulation of the function of CD56 tissue-resident or intratumoral NK cells.
人类自然杀伤 (NK) 细胞可分为两个亚群：CD56 和 CD56+NK 细胞，它们在成熟度、功能和分布上有所不同。调节 NK 细胞功能的机制尚未完全阐明。芳香烃受体 (AhR) 是一种配体激活的转录因子，可与多种内源性和外源性分子结合，最近已被证明可调节免疫细胞的功能和分化。在这里，我们研究了 AhR 的表达及其在调节 NK 细胞功能中的作用。我们发现 AhR mRNA 在周围血 CD56+NK 细胞中高度表达，并且随着 NK 细胞呈现出更成熟的表型，AhR mRNA 表达逐渐降低。CD56+NK 细胞对 AhR 配体高度敏感。具体而言，AhR 配体调节其激活及其 NK 细胞受体的表达，以及细胞因子分泌，这是这些细胞的主要功能。由于 CD56+NK 细胞在组织和肿瘤中高度富集，我们的观察结果表明局部 AhR 配体可能对调节 CD56 组织驻留或肿瘤内 NK 细胞的功能产生影响。
