title: Lipid abnormalities and lipid-based repair strategies in atopic dermatitis.
abstract: 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.
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, CA, USA. Electronic address: eliasp@derm.ucsf.edu.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000276:immunology*; D008055:Lipids / Q000276:immunology* / Q000627:therapeutic use*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008055:Lipids; D007073:Immunoglobulin E
keywords: Antimicrobial peptide; Atopic dermatitis; Barrier function; Filaggrin; Serine protease inhibitor; pH