Gruber, Robert, Boernchen, Christian, Rose, Katharina, Daubmann, Anne, Volksdorf, Thomas, Madykowski, Ewa, Vidal-y-Sy, Sabine, Peters, Eva M., Danso, Mogbekeloluwa, Bouwstra, Joke A., Hennies, Hans C., Moll, Ingrid, Schmuth, Matthias ORCID: 0000-0002-4064-1334 and Brandner, Johanna M. (2015). Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis. Am. J. Pathol., 185 (10). S. 2777 - 2790. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

Tight junctions are important for skin barrier function. The tight junction protein claudin 1 (Ctdn-1) has been reported to be down-regulated in nontesional skin of atopic dermatitis (AD) patients. In contrast, we did not observe a significant down-regulation of Ctdn-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gruber, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boernchen, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rose, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daubmann, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volksdorf, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madykowski, EwaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vidal-y-Sy, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, Eva M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danso, MogbekeloluwaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bouwstra, Joke A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hennies, Hans C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moll, IngridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmuth, MatthiasUNSPECIFIEDorcid.org/0000-0002-4064-1334UNSPECIFIED
Brandner, Johanna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-391330
DOI: 10.1016/j.ajpath.2015.06.021
Journal or Publication Title: Am. J. Pathol.
Volume: 185
Number: 10
Page Range: S. 2777 - 2790
Date: 2015
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1525-2191
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TIGHT JUNCTION PROTEINS; STRATUM-CORNEUM LIPIDS; SKIN BARRIER FUNCTION; HUMAN EPIDERMIS; CLAUDIN-1-DEFICIENT MICE; ICHTHYOSIS VULGARIS; FILAGGRIN; PSORIASIS; ECZEMA; KERATINOCYTESMultiple languages
PathologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39133

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