Molecular Mechanisms of Atopic Dermatitis Pathogenesis

Abstract

Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family's involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin's microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease's pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.

Keywords: allergic diseases; atopic dermatitis; epidermal barriers defects; genetic disorders; immunological disturbances; microbiome; pathogenesis; targeted therapies.

Figure 1

Epigenetic regulations dependent on environmental factors.

Figure 2

Immunological aberrations of atopic dermatitis. PRR (Pattern recognition receptors), PAMP (Pathogen-associated molecular patterns), CLR (C lectin receptors), PGLYRP (peptidoglycan recognition proteins), NOD (Nucleotide-binding oligomerization domain), TLR (Toll-like receptors), IL6 (Interleukin 6), IL12 (Interleukin 12),TSLP(Thymic stromal lymphopoietin), IL25 (Interleukin 25), IL33 (Interleukin 33), Th2 (T helper cells 2), IL4 (Interleukin 4), IL5 (Interleukin 5), IL13 (Interleukin 13), IL31 (Interleukin 31), Th1 (T helper cells 1), IL2(Interleukin 2), TNFα (Tumor necrosis factor alpha), INFγ (Interferon gamma), Th22 (T helper cells 22), IL22 (Interleukin 22), Th17 (T helper cells 17), IL17 (Interleukin 17).

Figure 3

S. aureus virulence factors & atopic skin susceptibility factors. PSMα (Phenol-soluble modulins alpha), KC (Keratinocytes), IL-1α (Interleukin 1α), IL-36α (Interleukin 36α), Tγδ (Gamma delta T cells), ILC3 (Type 3 innate lymphoid cells), IL-17 (Interleukin 17), N (Neutrophils), Rec. TNF (receptors for Tumor necrosis factor), ClfA (Clumping factors A), ClfB (clumping factors B), fnBP (Fibronectin-binding protein), IsdA (Iron-regulated surface determinant A), SCFA, PAMP (Pathogen-associated molecular patterns), TLR2 (Toll-like receptor 2), Th2(T helper cells 2), IL-4 (Interleukin 4), IL-13 (Interleukin 13), AMP (Antimicrobial peptides), IL-31 (Interleukin 31), SEA (Staphylococcal enterotoxin A), SEB (Staphylococcal enterotoxin B), SEC (Staphylococcal enterotoxin C), TSST1 (toxic shock syndrome toxin 1), L (Lymphocytes), M (Macrophages).

Figure 4

Therapies based on the pathogenesis of atopic dermatitis. TSLP(Thymic stromal lymphopoietin), IL25 (Interleukin 25), IL33 (Interleukin 33), Th2 (T helper cells 2), IL4 (Interleukin 4), IL5 (Interleukin 5), IL13 (Interleukin 13), IL31 (Interleukin 31), Th1 (T helper cells 1), IL2(Interleukin 2), TNFα (Tumor necrosis factor alpha), INFγ (Interferon gamma), Th22 (T helper cells 22), IL22 (Interleukin 22), Th17 (T helper cells 17), IL17 (Interleukin 17).