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

被引：139

作者：

Seumois, Gregory ^{[1
,2
,3
]}

Chavez, Lukas ^{[1
]}

Gerasimova, Anna ^{[1
]}

Lienhard, Matthias ^{[1
]}

Omran, Nada ^{[2
]}

Kalinke, Lukas ^{[2
]}

Vedanayagam, Maria ^{[2
]}

Ganesan, Asha Purnima V. ^{[2
]}

Chawla, Ashu ^{[1
]}

Djukanovic, Ratko ^{[2
]}

Ansel, K. Mark ^{[3
]}

Peters, Bjoern ^{[1
,4
]}

Rao, Anjana ^{[1
,2
,3
,5
]}

Vijayanand, Pandurangan ^{[1
,2
,3
]}

机构：

[1] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA

[2] Univ Southampton, Fac Med, Southampton Natl Inst Hlth Res, Resp Biomed Res Unit, Southampton SO9 5NH, Hants, England

[3] Univ Calif San Francisco, San Francisco, CA 94143 USA

[4] Sanford Consortium Regenerat Med, La Jolla, CA USA

[5] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 08期

关键词：

IMMUNITY; ACTIVATION; PLASTICITY; GENETICS; DATABASE; DISEASE; ALLERGY; SCALE; MYC;

D O I：

10.1038/ni.2937

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (T(H)2 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 T(H)1 cells and T(H)2 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 T(H)2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for T(H)2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human T(H)2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

引用

页码：777 / +

页数：15

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