Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
Toxicol Sci. 2014 Jun;139(2):350-61. doi: 10.1093/toxsci/kfu047. Epub 2014 Mar 27.
Epigenetic regulation of gene expression plays a pivotal role in the orchestration of immune responses and may determine the vigor, quality, or longevity of such responses. Chemical allergens can be divided into two categories: skin sensitizing chemicals associated with allergic contact dermatitis, and chemicals that cause sensitization of the respiratory tract and occupational asthma. In mice, these are characterized by different T helper cell responses. To explore the regulation and maintenance of these divergent responses, mice were exposed to 2,4-dinitrochlorobenzene (DNCB, a contact allergen) or trimellitic anhydride (TMA, a respiratory allergen). DNA from draining lymph nodes was processed for methylated DNA immunoprecipitation followed by hybridization to a whole-genome DNA promoter array. 6319 differently methylated regions (DMRs) were identified following DNCB treatment, whereas 2178 DMRs were measured following TMA treatment, with approximately half of the TMA DMRs common to DNCB. When limited to promoter region-associated DMRs, 637 genes were uniquely associated with DNCB-induced DMRs but only 164 genes were unique to TMA DMRs. Promoter-associated DMRs unique to either DNCB or TMA were generally hypomethylated whereas DMRs common to both allergens tended to be hypermethylated. Pathway analyses highlighted a number of immune-related pathways, including chemokine and cytokine signaling. These data demonstrate that chemical allergen exposure results in characteristic patterns of DNA methylation indicative of epigenetic regulation of the allergic response.
基因表达的表观遗传调控在免疫反应的协调中起着关键作用，并且可能决定这些反应的活力、质量或持久性。化学过敏原可分为两类：与过敏性接触性皮炎相关的皮肤致敏化学物质，以及引起呼吸道致敏和职业性哮喘的化学物质。在小鼠中，这些物质的特征是不同的辅助性 T 细胞反应。为了探索这些不同反应的调节和维持，用 2,4-二硝基氯苯（DNCB，一种接触过敏原）或均苯四甲酸酐（TMA，一种呼吸道过敏原）处理小鼠。用甲基化 DNA 免疫沉淀处理引流淋巴结的 DNA，然后用全基因组 DNA 启动子阵列杂交。DNCB 处理后鉴定出 6319 个差异甲基化区域（DMR），而 TMA 处理后测量到 2178 个 DMR，约一半的 TMA DMR 与 DNCB 共有。当仅限于启动子区域相关的 DMR 时，有 637 个基因与 DNCB 诱导的 DMR 特异性相关，而仅有 164 个基因与 TMA DMR 特异性相关。与 DNCB 或 TMA 相关的启动子相关 DMR 通常呈低甲基化，而两者共有的 DMR 则倾向于高甲基化。途径分析突出了许多与免疫相关的途径，包括趋化因子和细胞因子信号。这些数据表明，化学过敏原暴露导致 DNA 甲基化的特征模式，表明过敏反应的表观遗传调控。
