Cutting Edge: Innate production of IFN-gamma by NK cells is independent of epigenetic modification of the IFN-gamma promoter |
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Authors: | Tato Cristina M Martins Gislâine A High Frances A DiCioccio Catherine B Reiner Steven L Hunter Christopher A |
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Affiliation: | Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
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Abstract: | The ability of NK and T cells to produce IFN-gamma is critical for resistance to numerous intracellular pathogens but the kinetics of these responses differ. Consistent with this is a requirement for naive T cells to become activated and undergo proliferation-dependent epigenetic changes to the IFN-gamma locus that allow them to produce IFN-gamma. The data presented here reveal that unlike T cells, murine NK cells produce IFN-gamma under conditions of short-term cytokine stimulation, and these events are independent of proliferation and cell cycle progression. Furthermore, analysis of the IFN-gamma locus in NK cells reveals that this locus is constitutively demethylated. The finding that NK cells do not need to remodel the IFN-gamma locus to produce IFN-gamma, either because they do not exhibit epigenetic repression or they have undergone prior remodeling during development, provides a molecular basis for the innate and adaptive regulation of the production of this cytokine. |
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