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

Autor: Marco Garcia, Tessa Hunter, Arunima Kohli, Kari C. Nadeau, Leslie Cachola, Rachel L. Miller, R. Scott Runyon, Fred Lurmann, Ruth Krasnow, Gary E. Swan, Regina Ahn, Lisa M. Jack, Amanda Jacobson, Nitya Rajeshuni
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Heredity
Transcription
Genetic
Non-Clinical Medicine
Pulmonology
Gene Expression
Monozygotic twin
lcsh:Medicine
T-Lymphocytes
Regulatory
Epigenesis
Genetic
0302 clinical medicine
Molecular Cell Biology
Child
lcsh:Science
0303 health sciences
Multidisciplinary
T Cells
FOXP3
Forkhead Transcription Factors
Middle Aged
3. Good health
medicine.anatomical_structure
DNA methylation
Medicine
Female
Epigenetics
Environmental Health
Research Article
Adult
Adolescent
Regulatory T cell
Immune Cells
T cell
Immunology
Biology
Interferon-gamma
03 medical and health sciences
Genetics
medicine
Genetic predisposition
Humans
Genetic Predisposition to Disease
Aged
030304 developmental biology
Asthma
Inflammation
lcsh:R
Immunity
Twins
Monozygotic
DNA Methylation
medicine.disease
Genetic Loci
Genetics of Disease
CpG Islands
Gene-Environment Interaction
Tobacco Smoke Pollution
Clinical Immunology
lcsh:Q
Gene Function
T-Lymphocytes
Cytotoxic
030215 immunology
Zdroj: PLoS ONE, Vol 7, Iss 11, p e48796 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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