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Glucocorticoids regulate natural killer cell function epigenetically.

Justin L Eddy1, Karen Krukowski1, Linda Janusek2

  • 1Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.

Cellular Immunology
|July 1, 2014
PubMed
Summary
This summary is machine-generated.

Glucocorticoids have a dual effect on the immune system. This study reveals how glucocorticoids epigenetically reduce natural killer (NK) cell cytotoxicity while priming them for increased proinflammatory cytokine production.

Keywords:
EpigeneticGlucocorticoidsGranule constituentsNatural killer cellsProinflammatory cytokines

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Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • Glucocorticoids are known for their immune-suppressing effects.
  • However, they can also enhance immune responses, presenting a complex immunologic profile.

Purpose of the Study:

  • To investigate the molecular mechanisms behind the dichotomous immunologic effects of glucocorticoids.
  • To understand how glucocorticoids influence natural killer (NK) cell function.

Main Methods:

  • Analyzing histone acetylation and chromatin accessibility in NK cells treated with glucocorticoids.
  • Measuring mRNA and protein levels for key immune-related genes, including perforin, granzyme B, interferon gamma, and IL-6.

Main Results:

  • Glucocorticoid treatment reduced NK cell cytolytic activity by decreasing histone acetylation and expression of perforin and granzyme B.
  • Conversely, glucocorticoids increased histone acetylation and accessibility for interferon gamma and IL-6 regulatory regions.
  • This epigenetic modification primed NK cells for enhanced proinflammatory cytokine production upon stimulation.

Conclusions:

  • Glucocorticoids exert opposing epigenetic effects on NK cells.
  • They reduce NK cell cytotoxicity while simultaneously priming them for increased proinflammatory cytokine release.