二手烟与环境空气污染暴露相结合，与儿童 T 效应细胞中 IFNy 的 CpG 甲基化增加和 T 调节细胞中 Foxp3 的表达降低有关。
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.
机构信息
Department of Pediatric Allergy and Immunology, Stanford University, 269 Campus Drive, Stanford, CA, 94305, USA.
出版信息
Clin Epigenetics. 2012 Sep 25;4(1):17. doi: 10.1186/1868-7083-4-17.
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.
背景
二手烟（SHS）和环境空气污染（AAP）暴露与哮喘的患病率和严重程度增加以及免疫细胞的 DNA 修饰有关。在目前的研究中，我们研究了 SHS 和 AAP 与 T 细胞群体中干扰素-γ（IFN-γ）和叉头框蛋白 3（Foxp3）的 DNA 甲基化和表达之间的关系。
方法
从弗雷斯诺（高 AAP；n=62）和斯坦福，加利福尼亚（低 AAP；n=40）招募 7-18 岁的受试者，并分为 SHS 暴露（Fresno：n=31，Stanford：n=6）和非 SHS 暴露（nSHS；Fresno：n=31，斯坦福：n=34）组。从外周血中分离出 T 细胞，评估 IFN-γ（效应 T 细胞中）或 Foxp3（调节性 T 细胞中）的 DNA 甲基化和表达水平。
结果
分析表明，与 SHS 暴露相关的 IFN-γ和 Foxp3 的平均%CpG 甲基化显着增加（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），并且两种基因的平均转录水平显着降低（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 也与过度甲基化相关（IFN-γ：FSHS 与 SSHS，p<0.05；FnSHS 与 SnSHS，p<0.05；Foxp3：FSHS 与 SSHS，p<0.05；FnSHS 与 SnSHS，p<0.05）和两种基因的转录减少（IFN-γ：FSHS 与 SSHS，p<0.05；FnSHS 与 SnSHS，p<0.05；Foxp3：FSHS 与 SSHS，p<0.05；FnSHS 与 SnSHS，p<0.05）。AAP 和 SHS 暴露之间的平均甲基化无显着差异（IFN-γ：p=0.15; Foxp3：p=0.27），Foxp3 表达也无显着差异（p=0.08）; AAP 仅暴露受试者的 IFN-γ 表达显着降低（p<0.05）。
结论
SHS 和 AAP 暴露与 Teffs 中 IFN-γ 和 Tregs 中 Foxp3 的显着过度甲基化和表达降低有关。每个暴露对 DNA 修饰和哮喘发病机制的相对贡献值得进一步研究。
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