Skin barrier in atopic dermatitis: beyond filaggrin

Abstract

Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Figure 1

Expression of filaggrin (FLG), claudin 1 (CLDN1) and claudin 4 (CLDN4) in skin fragments of adults with atopic dermatitis (AD) stained by immunohistochemistry. (A) Skin fragments of healthy controls: FLG, CLDN1 and CLDN4. (B) Skin fragments of patients with AD, showing reduced expression of FLG, CLDN1 and CLDN4. (C) Expression of FLG, CLDN1 and CLDN 4 (area percentage) in the control group without AD (n=33) compared with patients with AD (n=25). (D) Correlation between disease severity (EASI) and the expression of the proteins in the skin barrier. The line represents the arithmetic mean of the expression of proteins in the skin barrier (percentage area). ** p≤0.01 and *** p≤0.001

Figure 2

Main components of innate immune system in epidermis and their role in atopic dermatitis (AD). Defects in Toll-like receptor 2 contribute to increased colonization and infection by S. aureus. Decreased AD expression of AMP (catelicidin-LL37 and β-defensin) also favors skin infections. Reduced plasmacytoid dendritic cells in skin injured areas by AD, facilitating certain viral skin infections. Reduced NK cells in AD. S. epidermidis increase the expression of human β-defensin by human keratinocytes through TLR2 signaling pathway. IDEC are increased in AD skin lesion. NOD1 changes are associated with elevated IgE levels in AD individuals. Changes in expression of NLRP1 gene were associated to AD severity Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), other bacteria, staphylococcal enterotox in, virus, Toll-like receptors (TLR), nucleotide-binding oligomerization domain-containing protein (NOD) NOD-like receptor protein (NLRP) β-defensina 1, HBD-2,3 e LL37, inflammatory dendritic epidermal cells (IDEC), plasmacytoid DC (pDC).