Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation.

ABSTRACT: Cross-regulation of Toll-like receptor (TLR) responses by cytokines is essential for effective host defense, avoidance of toxicity and homeostasis, but the underlying mechanisms are not well understood. Our comprehensive epigenomics approach to the analysis of human macrophages showed that the proinflammatory cytokines TNF and type I interferons induced transcriptional cascades that altered chromatin states to broadly reprogram responses induced by TLR4. TNF tolerized genes encoding inflammatory molecules to prevent toxicity while preserving the induction of genes encoding antiviral and metabolic molecules. Type I interferons potentiated the inflammatory function of TNF by priming chromatin to prevent the silencing of target genes of the transcription factor NF-κB that encode inflammatory

SUBMITTER: Park SH 

PROVIDER: S-EPMC5605457 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature