Skin barrier defects in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology that is dependent upon interactions between the host and the environment. Acute skin lesions exhibit the features of a Th2-driven inflammatory disorder, and many patients are highly atopic. The skin barrier plays key roles in immune surveillance and homeostasis, and in preventing penetration of microbial products and allergens. Defects that compromise the structural integrity or else the immune function of the skin barrier play a pivotal role in the pathogenesis of AD. This article provides an overview of the array of molecular building blocks that are essential to maintaining healthy skin. The basis for structural defects in the skin is discussed in relation to AD, with an emphasis on filaggrin and its genetic underpinnings. Aspects of innate immunity, including the role of antimicrobial peptides and proteases, are also discussed.

Figure 1. Schematic of the Immune Response in AD Skin Lesions

Defects in the epithelial barrier provide a portal of entry for microbial products and allergens. In conjunction, these antigens trigger the innate response through induction of cytokines from the epithelium. Together, these events orchestrate the induction of Th2 cells which secrete IL-4, IL-5, IL-13 and IL-31, production of IgE, and activation of basophils and mast cells. This process is highly dynamic and evolves to include hetereogeneous T-cell types including Th1 cells.

Figure 2. Structural and Immune Components Contributing to Barrier Defects in AD

The expanded view provides a schematic representation of the distribution of structural proteins and components of the innate immune system in the uppermost layers of the epidermis.