Innate immune factor gene expression profiles in patients with atopic dermatitis

Abstract

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.

Keywords

• atopic dermatitis
• cytokines
• toll-like receptors
• methylation
• innate immunity
• gene expression