Cutting Edge: Innate production of IFN-gamma by NK cells is independent of epigenetic modification of the IFN-gamma promoter.
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.
Tato
Cristina M
CM
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Martins
Gislâine A
GA
High
Frances A
FA
DiCioccio
Catherine B
CB
Reiner
Steven L
SL
Hunter
Christopher A
CA
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D002453:Cell Cycle; D002455:Cell Division; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D016654:Genes, RAG-1; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016853:Muromonab-CD3 / Q000494:pharmacology
D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016853:Muromonab-CD3; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D018664:Interleukin-12; D007371:Interferon-gamma