title: Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis.
abstract: Tight junctions are important for skin barrier function. The tight junction protein claudin 1 (Cldn-1) has been reported to be down-regulated in nonlesional skin of atopic dermatitis (AD) patients. In contrast, we did not observe a significant down-regulation of Cldn-1 in nonlesional skin of the AD cohort used in this study. However, for the first time, a significant down-regulation of Cldn-1 in the upper and lower epidermal layers of lesional skin was detected. In addition, there was a significant up-regulation of Cldn-4 in nonlesional, but not lesional, AD skin. For occludin, no significant alterations were observed. In an AD-like allergic dermatitis mouse model, Cldn-1 down-regulation in eczema was significantly influenced by dermal inflammation, and significantly correlated with hallmarks of eczema (ie, increased keratinocyte proliferation, altered keratinocyte differentiation, increased epidermal thickness, and impaired barrier function). In human epidermal equivalents, the addition of IL-4, IL-13, and IL-31 resulted in a down-regulation of Cldn-1, and Cldn1 knockdown in keratinocytes resulted in abnormal differentiation. In summary, we provide the first evidence that Cldn-1 and Cldn-4 are differentially involved in AD pathogenesis. Our data suggest a role of Cldn-1 in AD eczema formation triggered by inflammation.
authors: Department of Dermatology, Venerology, and Allergology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: r.gruber@i-med.ac.at.
authors: Robert
authors: R
authors: Gruber
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Christian
authors: C
authors: Börnchen
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Katharina
authors: K
authors: Rose
authors: Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Anne
authors: A
authors: Daubmann
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Thomas
authors: T
authors: Volksdorf
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Ewa
authors: E
authors: Wladykowski
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Sabine
authors: S
authors: Vidal-Y-Sy
authors: Department of Psychosomatic Medicine, Psychoneuroimmunology Laboratory, Justus-Liebig University, Giessen, Germany; Center for Internal Medicine and Dermatology, Charité-University Medicine, Berlin, Germany.
authors: Eva M
authors: EM
authors: Peters
authors: Department of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
authors: Mogbekeloluwa
authors: M
authors: Danso
authors: Department of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, the Netherlands.
authors: Joke A
authors: JA
authors: Bouwstra
authors: Department of Dermatology, Venerology, and Allergology, Medical University of Innsbruck, Innsbruck, Austria; Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors: Hans C
authors: HC
authors: Hennies
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Ingrid
authors: I
authors: Moll
authors: Department of Dermatology, Venerology, and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Matthias
authors: M
authors: Schmuth
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: brandner@uke.de.
authors: Johanna M
authors: JM
authors: Brandner
mesh_terms: D000328:Adult; D062445:Claudin-1 / Q000378:metabolism*; D062506:Claudin-4 / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D015603:Keratinocytes / Q000473:pathology*; D008297:Male; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D062506:Claudin-4; D018793:Interleukin-13