Alaskhar Alhamwe Bilal, Khalaila Razi, Wolf Johanna, von Bülow Verena, Harb Hani, Alhamdan Fahd, Hii Charles S, Prescott Susan L, Ferrante Antonio, Renz Harald, Garn Holger, Potaczek Daniel P
1Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, Hans-Meerwein-Straße 3, 35043 Marburg, Germany.
inVIVO Planetary Health, Group of the Worldwide Universities Network (WUN), New York, NJ USA.
Allergy Asthma Clin Immunol. 2018 May 23;14:39. doi: 10.1186/s13223-018-0259-4. eCollection 2018.
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.
本综述涵盖组蛋白修饰的基本方面以及翻译后组蛋白修饰在过敏性疾病发展中的作用,包括其发展背后的免疫机制。与DNA甲基化一起,组蛋白修饰(包括组蛋白乙酰化、甲基化、磷酸化、泛素化等)代表了经典的表观遗传机制。然而,在过敏背景下,与DNA甲基化相比,组蛋白修饰受到的关注要少得多。我们对文献进行了系统综述,以公正、全面地更新组蛋白修饰在过敏中的参与情况及其发展背后的机制。除了涵盖对组蛋白修饰在调节过敏性疾病发展中的作用日益增长的兴趣外,本综述还总结了一些支持这一作用的证据。组蛋白修饰的作用至少在两个层面上体现。一是对促成过敏性炎症的细胞(T细胞和巨噬细胞)以及参与气道重塑的细胞[(肌)成纤维细胞]的调节。另一个是组蛋白修饰与过敏表型之间的直接关联。组蛋白修饰酶抑制剂可能有潜力用作抗过敏药物。此外,表观遗传模式可能为过敏性疾病的诊断提供新工具。