Format

Send to

Choose Destination
Nat Immunol. 2014 Aug;15(8):777-88. doi: 10.1038/ni.2937. Epub 2014 Jul 6.

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

Author information

1
1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK. [3] University of California San Francisco, San Francisco, California, USA. [4].
2
1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2].
3
La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
4
Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
5
University of California San Francisco, San Francisco, California, USA.
6
1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Sanford Consortium for Regenerative Medicine, La Jolla, California, USA. [3] Department of Pharmacology, University of California San Diego, San Diego, California, USA. [4] University of California San Diego Moores Cancer Center, San Diego, California, USA.
7
1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK. [3] University of California San Francisco, San Francisco, California, USA.

Abstract

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Comment in

PMID:
24997565
PMCID:
PMC4140783
DOI:
10.1038/ni.2937
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center