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PMID: 23226205 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Asthma discordance in twins is linked to epigenetic modifications of T cells.

PloS one ·Vol. 7 ·No. 11 ·2012-00-00 ·Pages e48796

Runyon RS, Cachola LM, Rajeshuni N, Hunter T, Garcia M, Ahn R, Lurmann F, Krasnow R, Jack LM, Miller RL, Swan GE, Kohli A, Jacobson AC, Nadeau KC

Abstract

T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.

MeSH Terms
Adolescent Adult Aged Asthma/etiology,genetics,immunology,pathology Child CpG Islands DNA Methylation Epigenesis, Genetic Female Forkhead Transcription Factors/genetics,immunology Gene-Environment Interaction Genetic Loci Genetic Predisposition to Disease Humans Interferon-gamma/genetics,immunology Male Middle Aged T-Lymphocytes, Cytotoxic/immunology,metabolism,pathology T-Lymphocytes, Regulatory/immunology,metabolism,pathology Tobacco Smoke Pollution/adverse effects Transcription, Genetic Twins, Monozygotic/genetics
Chemicals
FOXP3 protein, human Forkhead Transcription Factors Tobacco Smoke Pollution Interferon-gamma
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Runyon R Scott
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Cachola Leslie M
Rajeshuni Nitya
Hunter Tessa
Garcia Marco
Ahn Regina
Lurmann Fred
Krasnow Ruth
Jack Lisa M
Miller Rachel L
Swan Gary E
Kohli Arunima
Jacobson Amanda C
Nadeau Kari C
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0048796
Published
2012-00-00
Epub
2012-00-30
Pages
e48796
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3511472
Subset
IM
Grants
NIAID NIH HHS · AI057229 · United States
NIDA NIH HHS · R01 DA011170 · United States
NIAID NIH HHS · U19 AI090019 · United States
NIDA NIH HHS · DA011170 · United States
NIAID NIH HHS · U19 AI057229 · United States
NIDA NIH HHS · R01 DA023063 · United States
NIAID NIH HHS · AI090019 · United States
NIDA NIH HHS · DA023063 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0048796 PMC Full Text View journal details
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