Lipid abnormalities and lipid-based repair strategies in atopic dermatitis

• Atopic dermatitis (AD) results from inherited abnormalities that impact epidermal barrier function.
• The paracellular barrier defect in AD is due to abnormal lipid composition, transport and organization.
• Barrier abnormality in AD also allows for pathogen and antigen access into epidermis.
• Increased serine protease activity accounts for decreased lipids and further decline in ceramides in AD.
• This emerging paradigm may lead to lipid-based approaches for corrective therapy in AD.

Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes atopic dermatitis (AD). We review here increasing evidence that the inflammation in AD results primarily from inherited abnormalities in epidermal structural and enzymatic proteins that impact permeability barrier function. We also will show that the barrier defect can be attributed to a paracellular abnormality due to a variety of abnormalities in lipid composition, transport and extracellular organization. Accordingly, we also review the therapeutic implications of this emerging pathogenic paradigm, including several current and potentially novel, lipid-based approaches to corrective therapy. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.