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
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References
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Journal ArticleDOI
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
The cornified envelope: a model of cell death in the skin
TL;DR: New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
Journal ArticleDOI
Claudin-based tight junctions are crucial for the mammalian epidermal barrier a lesson from claudin-1–deficient mice
Mikio Furuse,Masaki Hata,Kyoko Furuse,Yoko Yoshida,Akinori Haratake,Yoshinobu Sugitani,Tetsuo Noda,Tetsuo Noda,Akiharu Kubo,Shoichiro Tsukita +9 more
TL;DR: Findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.
Journal ArticleDOI
Claudins and epithelial paracellular transport.
TL;DR: Information is reviewed on the structure, function, and transcriptional and posttranslational regulation of the claudin family as well as of their evolutionarily distant relatives called the PMP22/EMP/MP20/claudin, or pfam00822, superfamily.
Journal ArticleDOI
Barrier Function of the Skin: “La Raison d'Être” of the Epidermis
TL;DR: More sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired, current work has focused on developing a more physiologic mix of lipids for topical application to skin.
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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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