Date Published: May 23, 2018
Publisher: BioMed Central
Author(s): Bilal Alaskhar Alhamwe, Razi Khalaila, Johanna Wolf, Verena von Bülow, Hani Harb, Fahd Alhamdan, Charles S. Hii, Susan L. Prescott, Antonio Ferrante, Harald Renz, Holger Garn, Daniel P. Potaczek.
This review covers basic aspects of histone modification and the role of posttranslational histone modifications in the development of allergic diseases, including the immune mechanisms underlying this development. Together with DNA methylation, histone modifications (including histone acetylation, methylation, phosphorylation, ubiquitination, etc.) represent the classical epigenetic mechanisms. However, much less attention has been given to histone modifications than to DNA methylation in the context of allergy. A systematic review of the literature was undertaken to provide an unbiased and comprehensive update on the involvement of histone modifications in allergy and the mechanisms underlying this development. In addition to covering the growing interest in the contribution of histone modifications in regulating the development of allergic diseases, this review summarizes some of the evidence supporting this contribution. There are at least two levels at which the role of histone modifications is manifested. One is the regulation of cells that contribute to the allergic inflammation (T cells and macrophages) and those that participate in airway remodeling [(myo-) fibroblasts]. The other is the direct association between histone modifications and allergic phenotypes. Inhibitors of histone-modifying enzymes may potentially be used as anti-allergic drugs. Furthermore, epigenetic patterns may provide novel tools in the diagnosis of allergic disorders.
In the last few decades, there has been a substantial increase in the prevalence of allergic diseases in the industrialized countries [1–3]. Since this change could not be explained by a rather stable population genetic profile [2–4], increased exposure to harmful and reduced exposure to protective epigenetically-mediated environmental factors have been considered, at least in part, as a possible explanation for this epidemiological phenomenon [5–9]. While DNA methylation has been extensively studied as the epigenetic mechanism involved in the etiopathogenesis of allergic disorders, posttranslational histone modifications, another important classical epigenetic mechanism, have not been as widely investigated and discussed because it is not considered as important as DNA methylation [5–7, 10]. The review firstly describes the (bio-) chemical basics of epigenetic histone modifications. This is followed by an assessment of recent evidence that supports a role for histone modifications in the epigenetic regulation of the pathogenesis of allergy and related disorders, together with a description of the underlying cellular and molecular mechanisms.
The results of our systematic literature assessment demonstrate a growing interest in the contribution of histone modifications in regulating the development of allergic disorders and, at the same time, provide evidence supporting this contribution. The role of histone modification is manifested at least at two levels. One involves the regulation of cells participating in the allergic inflammatory reaction, namely the inflammatory cells, T cells and macrophages, and the local tissue cells, such as (myo-) fibroblasts, which contribute to remodeling of airways. The other is the direct relationships between histone modifications and allergic phenotypes.