Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children

Clinical Epigenetics

Kari Nadeau²  S Katharine Hammond³  Olivier Humblet²  Christina Maher¹  Rachel L Miller⁴  Marco A Garcia²  Arunima Kohli² 

[1]Division of Pediatric Allergy and Immunology, Department of Pediatrics, Columbia University Medical Center, PH8E, 630 West 168th Street, New York, NY, 10032, USA

[2]Department of Pediatric Allergy and Immunology, Stanford University, 269 Campus Drive, Stanford, CA, 94305, USA

[3]Division of Environmental Health Sciences, University of California, 50 University Hall, Berkeley, CA, 94720, USA

[4]Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University Medical Center, PH8E, 630 West 168th Street, New York, NY, 10032, USA

关键词: T regulatory cells;    T effectors;    Pediatrics;    Epigenetic regulation;    Methylation;    Foxp3;    IFN-γ;    Ambient air pollution;    Secondhand smoke;   

Others  :  791308
DOI  :  10.1186/1868-7083-4-17

 received in 2012-06-16, accepted in 2012-08-29,  发布年份 2012

【 摘 要 】

Background

Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined the association between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN-γ) and forkhead box protein 3 (Foxp3) in T cell populations.

Methods

Subjects 7–18 years old were recruited from Fresno (high AAP; n = 62) and Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31, Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34) groups. T cells purified from peripheral blood were assessed for levels of DNA methylation and expression of IFN-γ (in effector T cells) or Foxp3 (in regulatory T cells).

Results

Analysis showed a significant increase in mean % CpG methylation of IFN-γ and Foxp3 associated with SHS exposure (IFN-γ: FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3: FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a significant decrease in mean transcription levels of both genes (IFN-γ: FSHS 0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75, FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated with hypermethylation (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased transcription of both genes (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average methylation between AAP- and SHS-only exposures was not significantly different (IFN-γ: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN-γ expression was significantly decreased in AAP-only subjects (p < 0.05).

Conclusions

Exposures to SHS and AAP are associated with significant hypermethylation and decreased expression of IFN-γ in Teffs and Foxp3 in Tregs. Relative contributions of each exposure to DNA modification and asthma pathogenesis warrant further investigation.

【 授权许可】

   
2012 Kohli et al.; licensee BioMed Central Ltd.

【 图 表 】

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