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Title: Neurotrophic Tyrosine Kinase Receptor 1 is Epigenetically Regulated by IL-13 and Contributes to Allergic Inflammation      
keywords:
Other
ID:
PRJNA247384
description:
Despite the well-recognized role of IL-13–induced transcriptional responses in allergic inflammation, the epigenetic mechanisms driven by IL-13 have not been well defined. We interrogated the transcriptional and epigenetic signatures of IL-13-induced epithelial responses focusing on the chromatin activation marks H3K4me3, H3K9Ac, and H3K27Ac. ChIP-sequencing analysis revealed that IL-13–inducible genes were epigenetically poised for induction and continued to accumulate epigenetic changes in response to IL-13. By intersecting the transcriptome and the epigenome of the IL-13 response, we identified neurotrophic tyrosine kinase receptor 1 (NTRK1) as a major target of IL-13 in epithelial cells. Using eosinophilic esophagitis as a model system for human allergic inflammation, we found that NTRK1 was dramatically induced in inflamed esophageal biopsies, and downstream mediators of NTRK1 signaling were elevated in diseased tissue. The NTRK1 ligand nerve growth factor (NGF) was constitutively expressed in control and disease states, indicating that induction of the receptor by IL-13 limited pathway activation. In epithelial cells, NGF and IL-13 synergistically induced transcription and secretion of the key eosinophil chemoattractant CCL26 (eotaxin-3). In summary, we demonstrate that IL-13–mediated allergic responses are epigenetically driven and identify NTRK1 as a novel epigenetic and transcriptional target of IL-13 that uniquely contributes to allergic inflammation. Overall design: Human esophageal epithelial cell line TE-7 was stimulated with IL-13 at 100 ng/ml for 2 hr, 6 hr and 24 hr and subjected to RNA-sequencing. In parallel, TE-7 cells were induced with IL-13 for 6 hr and subjected to ChIP-sequencing analysis for H3K4me3, H3K9Ac and H3K27Ac activating chromatin marks.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA247384
authentication:
none
authorization:
none
ID:
pmid:25389033
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • P30 DK078392/DK/NIDDK NIH HHS/United States

  • R37 AI045898/AI/NIAID NIH HHS/United States

  • T35 DK060444/DK/NIDDK NIH HHS/United States

  • R01 AI083450/AI/NIAID NIH HHS/United States

  • K22 HL098691/HL/NHLBI NIH HHS/United States

  • UL1 TR000077/TR/NCATS NIH HHS/United States

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