Journal ArticleDOI
The skin: an indispensable barrier
TLDR
Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis.Abstract:
The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitisread more
Citations
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Journal ArticleDOI
The skin microbiome
TL;DR: An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.
Journal ArticleDOI
UV Radiation and the Skin
TL;DR: Developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance are targeted.
Journal ArticleDOI
Skin immune sentinels in health and disease
TL;DR: This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease and newly identified CD103+ dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens.
Journal ArticleDOI
Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness
TL;DR: Caution should still be exercised when new sunscreens are developed and research that includes sunscreen NP stabilization, chronic exposures, and reduction of NPs' free-radical production should receive full attention.
Journal ArticleDOI
Epidermal Barrier Dysfunction in Atopic Dermatitis
Michael J. Cork,Simon G. Danby,Yiannis Vasilopoulos,Jonathan Hadgraft,Majella E. Lane,Manar Moustafa,Manar Moustafa,Richard H. Guy,Alice Macgowan,Rachid Tazi-Ahnini,Simon J. Ward +10 more
TL;DR: The strong association between both genetic barrier defects and environmental insults to the barrier with AD suggests that epidermal barrier dysfunction is a primary event in the development of this disease.
References
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Journal ArticleDOI
Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris
Frances J.D. Smith,Alan D. Irvine,Ana Terron-Kwiatkowski,Aileen Sandilands,Linda E. Campbell,Yiwei Zhao,Haihui Liao,Alan Evans,David Goudie,Sue Lewis-Jones,Gehan Arseculeratne,Colin S. Munro,Ann Sergeant,Grainne M. O'Regan,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Richard B. Presland,Philip Fleckman,W.H. Irwin McLean +20 more
TL;DR: It is found that loss or reduction of this major structural protein, filaggrin, leads to varying degrees of impaired keratinization.
Book ChapterDOI
Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier
TL;DR: Further elucidation of the molecular architecture and interactions of lipid and nonlipid components of the stratum corneum intercellular domains will be a prerequisite for a comprehensive understanding of stratum Corneum function.
Journal ArticleDOI
ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation.
Thorsten Maretzky,Karina Reiss,Andreas Ludwig,Julian Buchholz,Felix Scholz,Erhardt Proksch,Bart De Strooper,Dieter H. Hartmann,Paul Saftig +8 more
TL;DR: It is shown that E-cadherin is cleaved specifically by ADAM (a disintegrin and metalloprotease) 10 in its ectodomain, and the data strongly suggest that this protease constitutes a major regulatory element for the multiple functions of E-bodies under physiological as well as pathological conditions.
Journal ArticleDOI
Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins
Rainer Zenz,Robert Eferl,Lukas Kenner,Lore Florin,Lars Hummerich,Denis Mehic,Harald Scheuch,Peter Angel,Erwin Tschachler,Erwin F. Wagner +9 more
TL;DR: It is proposed that the abrogation of JunB/activator protein 1 (AP-1) in keratinocytes triggers chemokine/cytokine expression, which recruits neutrophils and macrophages to the epidermis thereby contributing to the phenotypic changes observed in psoriasis.
Journal ArticleDOI
Bricks and mortar of the epidermal barrier
Zoltán Nemes,Peter M. Steinert +1 more
TL;DR: A number of diseases which display defective epidermal barrier function are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.
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Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
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