The aryl hydrocarbon receptor modulates the function of human CD56^bright NK cells

Human natural killer (NK) cells are divided into two subsets: CD56^bright and CD56^dim 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^bright NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56^bright 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^bright 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^bright tissue-resident or intratumoral NK cells.