Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis

Abstract

The human skin can be affected by a multitude of diseases including inflammatory conditions such as atopic dermatitis and psoriasis. Here, we describe how skin barrier integrity and immunity become dysregulated during these two most common inflammatory skin conditions. We summarise recent advances made in the field of the skin innate immune system and its interaction with adaptive immunity. We review gene variants associated with atopic dermatitis and psoriasis that affect innate immune mechanisms and skin barrier integrity. Finally, we discuss how current and future therapies may affect innate immune responses and skin barrier integrity in a generalized or more targeted approach in order to ameliorate disease in patients.

FIGURE 1

Schematic representation of skin and underlying processes during steady state, psoriasis and atopic dermatitis. In psoriatic lesions increased cell proliferation occurs in the epidermis and elevated production of anti‐microbial peptides (AMPs), while during AD the skin barrier is impaired, which leads to increased allergen penetration, reduced natural moisturising factor (NMF) and may affect AMP abundance or activity. Both diseases are characterised by changes in microbiome composition. During psoriasis pro‐inflammatory T_H1 and T_H17 cells dominate the affected skin. In contrast, type 2‐associated cells, including T_H2 cells, eosinophils, basophils and ILC2 can increase during AD. GWAS analysis (publicly available databases: GWAS database, https://www.ebi.ac.uk/gwas/; GWAS Central, https://www.gwascentral.org/; accessed 15.11.2021; filtered for psoriasis and atopic eczema traits) of the most common SNPs associated with psoriasis (Pso) and atopic dermatitis (AD) are summarised in the Venn diagram