哮喘联盟

   摘要
   DNA甲基化参与辅助性T细胞（Th）成熟，而在肥胖相关哮喘中观察到的非过敏性Th1细胞极化系统炎症中,它是否存在潜在的调节异常作用尚不清楚。我们在8例青春期前肥胖哮喘儿童的外周血单核细胞（PBMCs）中研究表观基因组DNA甲基化情况，并与单纯哮喘患儿、单纯肥胖患儿和健康对照儿童的PBMCs中甲基化情况进行比较。不同的甲基化位点表明确定的生物学相关分子和通路。肥胖哮喘儿童的PBMCs有特异性DNA甲基化模式，包括启动子CCL5, IL2RA 和TBX21甲基化降低，基因编码连接Th1细胞极化的蛋白，启动子FCER2甲基化增加，IgE受体和TGFB1低亲和力，Th细胞活化抑制物。T细胞信号和巨噬细胞活化是肥胖哮喘选择性低甲基化的两条主要通路。结果提示,DNA甲基化调节异常与小儿肥胖相关哮喘中可见的非过敏性炎症有关。
 

（苏楠 审校）
Sci Rep. 2013 Jul 16;3:2164. doi: 10.1038/srep02164.

 

Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma.
 

Rastogi D, Suzuki M, Greally JM.
 

Abstract
While DNA methylation plays a role in T-helper (Th) cell maturation, its potential dysregulation in the non-atopic Th1-polarized systemic inflammation observed in obesity-associated asthma is unknown. We studied DNA methylation epigenome-wide in peripheral blood mononuclear cells (PBMCs) from 8 obese asthmatic pre-adolescent children and compared it to methylation in PBMCs from 8 children with asthma alone, obesity alone and healthy controls. Differentially methylated loci implicated certain biologically relevant molecules and pathways. PBMCs from obese asthmatic children had distinctive DNA methylation patterns, with decreased promoter methylation of CCL5, IL2RA and TBX21, genes encoding proteins linked with Th1 polarization, and increased promoter methylation of FCER2, a low-affinity receptor for IgE, and of TGFB1, inhibitor of Th cell activation. T-cell signaling and macrophage activation were the two primary pathways that were selectively hypomethylated in obese asthmatics. These findings suggest that dysregulated DNA methylation is associated with non-atopic inflammation observed in pediatric obesity-associated asthma.
 

Sci Rep. 2013 Jul 16;3:2164. doi: 10.1038/srep02164.