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Defining the AHR-regulated transcriptome in NK cells reveals gene expression programs relevant to development and

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The aryl hydrocarbon receptor (AHR) regulates natural killer (NK) cell function. AHR activation alters gene expression, impacting NK cell metabolism and immunity, offering potential therapeutic targets for immune suppression.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • The aryl hydrocarbon receptor (AHR) is a transcription factor influencing cancer and immunity.
  • Its specific transcriptional targets in natural killer (NK) cells are not well understood.

Purpose of the Study:

  • To identify genes directly regulated by AHR in NK cells.
  • To understand AHR's role in NK cell activation, phenotype, and function.

Main Methods:

  • RNA sequencing and chromatin immunoprecipitation sequencing (ChIP-seq) were performed on NK cells.
  • NK cells were treated with AHR agonists and antagonists.

Main Results:

  • AHR expression is induced by Stat3 during IL-21 activation, correlating with CD56bright phenotype.
  • AHR activation altered expression of 97 genes, impacting metabolism and oxidative stress.
  • 160 genes were identified as directly regulated by AHR, including NCAM1, KIT, and CYP1B1.

Conclusions:

  • AHR plays a significant role in regulating NK cell gene expression and function.
  • AHR and Stat3 may be coregulated in NK cells.
  • Targeting AHR pathways could overcome AHR-mediated immune suppression.