Chemical Allergen Induced Perturbations of the Mouse Lymph Node DNA Methylome

Abstract

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.

Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study

“…Epigenetic factors, such as DNA methylation, and sperm RNAs have been explored as potentially sensitive indicators of toxicity in different tissues (Dong et al , 2008; Boellmann et al , 2010; Chapman et al , 2014; Chappell et al , 2014; Conti et al , 2014; Koczor et al , 2015; Ozden et al , 2015; Chen et al , 2016; Dere et al , 2016). Transmission of epigenetic marks in the germ line has garnered attention recently due to increasing evidence of transgenerational inheritance and increased risk factors of developing diseases associated with such alterations (Guerrero-Bosagna et al , 2010; Manikkam et al , 2013; Skinner et al , 2013; Tracey et al , 2013).…”

Skin and respiratory chemical allergy: confluence and divergence in a hybrid adverse outcome pathway

“…It is early days, but there is reason to believe that immune responses to contact and chemical respiratory display differential patterns of gene expression and of epigenetic signatures. 58,[206][207][208] The differences in the AOPs to skin sensitisation and sensitisation of the respiratory tract do not immediately offer the basis for the development of novel approaches for the selective identification of respiratory allergens, or for distinguishing between contact and respiratory allergens. However, an appreciation of nodes in the pathway where differences may originate does suggests areas that are worthy of an investment (or a continued investment) in research.…”

T helper cell 2 immune skewing in pregnancy/early life: chemical exposure and the development of atopic disease and allergy

“…The epigenetic control of T‐cell maturation has been reviewed and summarized by Martino and Prescott . Moreover, the potential impact of epigenetic regulation of Th1/Th2 responses to skin‐sensitizing chemicals has been described recently . Methylation of IFNG is the main epigenetic mechanism of control of Th1 expression.…”