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

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).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).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.Exposure to secondhand smoke (SHS) is associated with a number of adverse health effects, including cancer, cardiovascular disease, and increased frequency and severity of respiratory disease [1]. Per the US Surgeon General’s 2006 report, any exposure to SHS results in increased health risks [1