Academic Commons

Articles

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

Kohli, Arunima; Garcia, Marco; Miller, Rachel L.; Maher, Christina; Humblet, Olivier; Hammond, S. Katharine; Nadeau, Kari

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.

Files

  • thumnail for 10a8c4601dda392a3374a8bc675d15f3.zip 10a8c4601dda392a3374a8bc675d15f3.zip binary/octet-stream 442 KB Download File

Also Published In

Title
Clinical Epigenetics
DOI
https://doi.org/10.1186/1868-7083-4-17

More About This Work

Academic Units
Medicine
Publisher
BioMed Central
Published Here
September 8, 2014

Notes

Secondhand smoke, Ambient air pollution, IFN-γ, Foxp3, Methylation, Epigenetic regulation, Pediatrics, T effectors, T regulatory cells