The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells. journal of experimental medicine Zhang, L. H., Shin, J. H., Haggadone, M. D., Sunwoo, J. B. 2016; 213 (11): 2249-2257


A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut. In this study, we show that liver-resident NK (NK1.1(+)CD3(-)) cells, defined as CD49a(+)TRAIL(+)CXCR6(+)DX5(-) cells in the mouse liver, constitutively express AhR. In AhR(-/-) mice, there is a significant reduction in the proportion and absolute number of these cells, which results from a cell-intrinsic dependence on AhR. This deficiency in liver-resident NK cells appears to be the result of higher turnover and increased susceptibility to cytokine-induced cell death. Finally, we show that this deficiency has functional implications in vivo. Upon hapten exposure, AhR(-/-) mice are not able to mount an NK cell memory response to hapten rechallenge. Together, these data demonstrate the requirement of AhR for the maintenance of CD49a(+)TRAIL(+)CXCR6(+)DX5(-) liver-resident NK cells and their hapten memory function.

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