The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells

Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim 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, tha...

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Bibliographic Details
Published in:European journal of immunology 2018-05, Vol.48 (5), p.771-776
Main Authors: Moreno‐Nieves, Uriel Y., Mundy, David C., Shin, June Ho, Tam, Kenric, Sunwoo, John B.
Format: Article
Language:English
Subjects:
AhR
Gene expression
Hydrocarbons
Innate immunity
Ligands
Lymphocyte receptors
Molecular chains
Natural killer cells
NK cell
NKG2D
NKp44
Phenotypes
Receptor mechanisms
Tumors
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Summary:Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim 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 CD56bright NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56bright 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 CD56bright 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 CD56bright tissue‐resident or intratumoral NK cells. Immature CD56bright NK cells highly express AhR, which modulates important processes, such as activation, receptor expression and cytokine secretion. Given that numerous AhR ligands exist (endogenous and exogenous), our observation indicates that the regulation of CD56bright NK cells may be more complex than previously thought.
ISSN:0014-2980
1521-4141
1521-4141
DOI:10.1002/eji.201747289