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

Bystritskaya, Elizaveta; Мурашкин, Н. Н.; Материкин, А. И.; Наумова, Е. А.; Свитич, О. А.

doi:10.33029/0206-4952-2022-43-3-255-265

Cited by 2 publications

(1 citation statement)

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“…Increased levels of all suggested molecules may be an evidence of Th2 immune response enhancement in the acute phase of the dermatitis, which is, in fact, an acknowledged classic model of the systemic AD pathogenesis. Nevertheless, our previous studies showed that at the same time there might be a difference at the local level (in the skin), where the inflammation takes place and anti-inflammatory mechanisms prevail [2]. Targeted expression analysis revealed that in the skin samples the expression of TLR9 and IL4 was 12 times significantly lower (p < 0.0001, p < 0.0005) in the lesional skin; and there was a 6-fold decrease in case of TLR2 (p < 0.01).…”

Section: Resultsmentioning

confidence: 94%

Innate immune factor gene expression profiles in patients with atopic dermatitis

Bystritskaia,

Murashkin,

Olisova

et al. 2023

Med. immunol.

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Atopic dermatitis is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronically relapsing dermatitis, age-related features of localization and morphology of lesions. The pathogenesis of atopic dermatitis is complex and includes epigenetic alterations, involved in the genomic adaptation, immune response reactions and dysfunction of the epithelial barrier that together trigger the development of atopic dermatitis. The aim of this study is to detect the expression level for IL4, IL13, IL33, TLR2, TLR9 genes in the biological materials of atopic patients.The targeted genes for further expression evaluation were selected according to our previous findings on genome-wide methylation study. We detected the cascades with the differentially methylated genes that are most likely to take place in atopic dermatitis. Thus, we investigated expression levels for the IL4, IL13, IL33, TLR2, TLR9 genes in the skin, peripheral blood mononuclear cells and whole blood cells using RT-PCR on 55 pediatric patients and 26 healthy volunteers, and on 50 adult patients. Statistical analysis was performed with the use of Kruskal-Wallis H test and Mann-Whitney U test. Targeted expression analysis revealed that in the skin samples the expression of TLR9 and IL4 was 12 times significantly lower (p < 0.0001, p < 0.0005) in the lesional skin; and there was a 6-fold decrease in case of TLR2 (p < 0.01). The results for blood mononuclear cells differed and expression levels for most of the assessed targets were significantly higher before treatment. We have also found out that those differences were strongly pronounced especially in an elder age group (12-18 y.o.). Studying the IL33 gene expression in the whole blood samples of adults revealed that its level was significantly higher in case of patients with moderate form of AD. Besides, we concluded that locally in the affected skin inflammatory immune response may dominate; in the mononuclear cells Th2 immune response apparently takes place. New insights on immunological markers and links among them may shed a light on atopic dermatitis pathogenic mechanisms. The detected molecules could play role as potential therapeutic targets and form a management approach for patients with atopic dermatitis.

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Section: Resultsmentioning

confidence: 94%

Innate immune factor gene expression profiles in patients with atopic dermatitis

Bystritskaia,

Murashkin,

Olisova

et al. 2023

Med. immunol.

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DNA methylation profile and expression of the phyllagrin gene in patients with atopic dermatitis: case-control study

Antonova,

Ufimtseva,

Makeev

et al. 2024

Vestnik dermatologii i venerologii

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Background: Atopic dermatitis (AtD) is one of the most common inflammatory skin diseases, affecting up to 20,0% of children and 2,0–8,0% of adults worldwide. Patients with atopic dermatitis usually have dry skin and itching, they are at higher risk of developing asthma, as well as allergic rhinitis. Features of the clinical course of AtD are associated with both interaction of genes and influence of environmental factors. Studying epigenetic mechanisms could provide understanding of the most likely mechanisms by which environmental factors influence gene expression and contribute to the development of AtD. The aim of the study is to conduct a comprehensive molecular genetic analysis (assessment of the level of global DNA methylation and expression of the filaggrin gene (FLG)) in patients with moderate to severe AtD. Material and methods: The case-control study was conducted from January, 2022, through June 2022. A total of 32 patients with AtD and 6 healthy volunteers were recruited. The level of global DNA methylation in blood samples of patients with AtD and healthy individuals was assessed. The filaggrin gene (FLG) expression was measured by polymerase chain reaction in blood samples. Results: A hypermethylation of the genome in patients with AtD is 2.3 times higher than the methylation of genome in controls (p=0,003). FLG gene (exon 3 position 7-8 and exon 1) expression in patients with AtD is decreased compared to control group. Conclusion: Interaction between genomic changes which are associated with mutations in key barrier and immune genes and environmental factors plays a fundamental role in the AtD pathogenesis. The current study found that the epigenome of AtD patients differs from healthy individuals. The study of pathogenetic mechanisms is the basis for the development of new methods of targeted therapy for this socially significant dermatosis.

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

Cited by 2 publications

References 4 publications

Innate immune factor gene expression profiles in patients with atopic dermatitis

Innate immune factor gene expression profiles in patients with atopic dermatitis

DNA methylation profile and expression of the phyllagrin gene in patients with atopic dermatitis: case-control study

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