Genome-wide DNA methylation profi le and expression of TLR2, TLR9, IL4, IL13 genes in pediatric patients with atopic dermatitis

Abstract

Introduction. Atopic dermatitis (AD) is a multifactorial disease, resulted from complex interactions between genetic and environmental factors. Epigenetic mechanisms involved in the gene expression regulationmay clarify how environmental exposure affects the risk of allergy development.

The aim of this study is to conduct a comprehensive analysis of the immune mechanisms (methylome; gene expression profile of TLR2, TLR9, IL4, IL13) locally and systematically in pediatric patients with moderate and severe AD.

Material and methods. With the use of DNA new generation sequencing technology (Oxford Nanopore Technologies Ltd) we performed a DNA methylation genome-wide study in atopic patients’ biopsies. At the same time the expression level for genes TLR2, TLR9, IL4, IL13 was assessed in the skin and mononuclear blood cells using real-time polymerase chain reaction.

Results. Targeted gene expression analysis revealed a significant (p ≤ 0.017) increase in the levels of TLR2, TLR9, IL4, IL13 expression in the blood of patients with AD compared with the group of comparison, as well as a decrease (p ≤ 0.05) in the levels of TLR2, TLR9, IL4 expression in affected skin compared to the group of comparison. We detected loci that were differentially methylated in atopic patients and healthy donors.

Conclusion. It is important to have a complete understanding of the AD pathogenic mechanisms. New insights on epigenetic and immunological markers associated with the risk of AD development will help to create new prognostic approaches in the management of patients with atopic pathology.

Keywords:atopic dermatitis; innate immunity; cytokines; Toll-like receptors; gene expression; methylation

For citation: Bystritskaya E.P., Murashkin N.N., Materikin A.I., Naumova E.A., Svitich O.A. Genome-wide DNA methylation profile and expression of TLR2, TLR9, IL4, IL13 genes in pediatric patients with atopic dermatitis. Immunologiya. 2022; 43 (3): 255–65. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-255-265 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. Authors declare no conflict of interests.

Authors’ contribution. The concept and design of the study, analysis of results – Svitich O.A., Murashkin N.N.; providing a database of clinical samples from patients – Materikin A.I.; bioinformatic processing of sequencing data, interpretation of the statistical analysis results – Naumova E.A.; conducting the experimental part of the research, statistical analysis and interpretation of its results – Bystritskaya E.P.

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EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Вскрытие
Medicine today

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