Epigenetic Mechanisms in Allergy Development and Prevention

Potaczek, Daniel P.; Alashkar Alhamwe, Bilal; Miethe, Sarah; Garn, Holger

doi:10.1007/164_2021_475

Daniel P. Potaczek¹⁴,
Bilal Alashkar Alhamwe^15,16,
Sarah Miethe¹⁴ &
…
Holger Garn¹⁴

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 268))

2622 Accesses
13 Citations

Abstract

There has been a substantial increase in the incidence and the prevalence of allergic disorders in the recent decades, which seems to be related to rapid environmental and lifestyle changes, such as higher exposure to factors thought to exert pro-allergic effects but less contact with factors known to be associated with protection against the development of allergies. Pollution is the most remarkable example of the former, while less contact with microorganisms, lower proportion of unprocessed natural products in diet, and others resulting from urbanization and westernization of the lifestyle exemplify the latter. It is strongly believed that the effects of environmental factors on allergy susceptibility and development are mediated by epigenetic mechanisms, i.e. biologically relevant biochemical changes of the chromatin carrying transcriptionally-relevant information but not affecting the nucleotide sequence of the genome. Classical epigenetic mechanisms include DNA methylation and histone modifications, for instance acetylation or methylation. In addition, microRNA controls gene expression at the mRNA level. Such epigenetic mechanisms are involved in crucial regulatory processes in cells playing a pivotal role in allergies. Those include centrally managing cells, such as T lymphocytes, as well as specific structural and effector cells in the affected organs, responsible for the local clinical presentation of allergy, e.g. epithelial or airway smooth muscle cells in asthma. Considering that allergic disorders possess multiple clinical (phenotypes) and mechanistic (endotypes) forms, targeted, stratified treatment strategies based on detailed clinical and molecular diagnostics are required. Since conventional diagnostic or therapeutic approaches do not suffice, this gap could possibly be filled out by epigenetic approaches.

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Abbreviations

A. lwoffii :: Acinetobacter lwoffii
AD:: Atopic dermatitis
AHR:: Airway hyperresponsiveness
APCs:: Antigen-presenting cells
AR:: Allergic rhinitis
BET:: Bromo- and extraterminal
CB:: Cord blood
DEPs:: Diesel exhaust particles
DNMT:: DNA methyltransferase
DUBs:: Deubiquitinating enzymes
FOXP3 (FOXP3):: Forkhead box protein 3 (gene)
GATA3:: GATA binding protein 3
HATs:: Histone acetyltransferases
HDACis:: HDAC inhibitors
HDACs:: Histone deacetylases
HDMs:: Histone demethylases
HMTs:: Histone methyltransferases
HRVs:: Human rhinoviruses
IFN-γ (IFNG):: Interferon-γ (gene)
IgE:: Immunoglobulin E
IL:: Interleukin
ILCs:: Innate lymphoid cells
MAP:: Mitogen-activated protein
MBD:: Methyl-CpG binding protein
MeCP2:: Methyl-CpG binding protein 2
miRNA:: microRNA
NECs:: Nasal epithelial cells
NO₂:: Nitrogen dioxide
NOS1–3 :: Nitric oxide 1–3 synthase genes
PAHs:: Polycyclic aromatic hydrocarbons
PBMCs:: PB mononuclear cells
PKCζ:: Protein kinase C, zeta
RISC:: RNA-induced silencing complex
RORC2 (RORγT):: RAR related orphan receptor C, isoform 2
SAM:: S-adenosyl-l-methionine
SCFAs:: Short-chain fatty acids
SO₂:: Sulfur dioxide
TBX21:: T-box 21 (T-bet)
TET1 (TET1):: Tet (10–11 translocation) methylcytosine dioxygenase 1 (gene)
TFs:: Transcription factors
Th:: T helper
Tregs:: Regulatory T cells

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Acknowledgments

Bilal Alashkar Alhamwe is supported by the German Academic Exchange Service (DAAD; Personal Reference no. 91559386) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; Grant 416910386–GRK 2573/1).

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Authors and Affiliations

Translational Inflammation Research Division and Core Facility for Single Cell Multiomics, Member of the German Center for Lung Research (DZL) the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps-University Marburg, Marburg, Germany
Daniel P. Potaczek, Sarah Miethe & Holger Garn
Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps-University Marburg, Marburg, Germany
Bilal Alashkar Alhamwe
College of Pharmacy, International University for Science and Technology (IUST), Daraa, Syria
Bilal Alashkar Alhamwe

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Daniel P. Potaczek
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Bilal Alashkar Alhamwe
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Sarah Miethe
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Holger Garn
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Correspondence to Holger Garn .

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Department of Environmental Medicine, University Augsburg, Medical Faculty, Augsburg, Germany
Claudia Traidl-Hoffmann
Charité - Universitätsmedizin Berlin, Klinik für Dermatologie, Berlin, Berlin, Germany
Torsten Zuberbier
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hanover, Germany
Thomas Werfel

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Potaczek, D.P., Alashkar Alhamwe, B., Miethe, S., Garn, H. (2021). Epigenetic Mechanisms in Allergy Development and Prevention. In: Traidl-Hoffmann, C., Zuberbier, T., Werfel, T. (eds) Allergic Diseases – From Basic Mechanisms to Comprehensive Management and Prevention . Handbook of Experimental Pharmacology, vol 268. Springer, Cham. https://doi.org/10.1007/164_2021_475

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DOI: https://doi.org/10.1007/164_2021_475
Published: 06 July 2021
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-84047-1
Online ISBN: 978-3-030-84048-8
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