Journal ArticleDOI
The skin: an indispensable barrier
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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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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.
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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.
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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.
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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
Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: A tight junction disease
Smail Hadj-Rabia,Lekbir Baala,Pierre Vabres,D. Hamel-Teillac,Emmanuel Jacquemin,Monique Fabre,Stanislas Lyonnet,Yves de Prost,Arnold Munnich,Michelle Hadchouel,Asma Smahi +10 more
TL;DR: Lack of claudin-1 in NISCH syndrome may lead to increased paracellular permeability between epithelial cells, and ZO-2-associated hypercholanemia emphasizes the role played by TJ components in hereditary cholestasis.
Journal ArticleDOI
Evidence That the Corneocyte Has a Chemically Bound Lipid Envelope
TL;DR: From the results of in situ derivatization of these lipids and the construction of molecular models, it is inferred that the bound lipids exist in ester linkage with protein on the surface of the corneocyte envelope and form a lipid envelope for each corneocytes.
Journal ArticleDOI
Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.
David P. Kelsell,Elizabeth E. Norgett,H Unsworth,Muy-Teck Teh,Thomas Cullup,Charles A. Mein,Patricia J.C. Dopping-Hepenstal,Beverly A. Dale,Gianluca Tadini,Philip Fleckman,Karen Stephens,Virginia P. Sybert,Susan B. Mallory,Bernard V. North,David R. Witt,Eli Sprecher,Aileen Taylor,Andrew Ilchyshyn,Cameron T. C. Kennedy,Helen Goodyear,Celia Moss,D. Paige,John I. Harper,Bryan D. Young,Irene M. Leigh,Robin A.J. Eady,Edel A. O'Toole +26 more
TL;DR: Sequencing of the ABCA12 gene revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI, which paves the way for early prenatal diagnosis and leads to a better understanding of epidermal differentiation and barrier formation.
Journal ArticleDOI
Skin barrier function, epidermal proliferation and differentiation in eczema
TL;DR: Common treatment strategies for eczema include the application of lipid-based creams and ointments, which aim toward the restoration of the defective permeability barrier, thus helping to normalize proliferation and differentiation.
Journal ArticleDOI
Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment
TL;DR: The stratum corneum has the ability to respond to changes in external humidity by altering the level of the strum corneum where it converts its reserves of filaggrin into water binding amino acids, such that under humid conditions water binding components will be produced in only the most superficial stratum Corneum, or even not produced at all.
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