Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis

Robert Gruber, Christian Börnchen, Katharina Rose, Anne Daubmann, Thomas Volksdorf, Ewa Wladykowski, Sabine Vidal-Y-Sy, Eva M. Peters, Mogbekeloluwa Danso, Joke A. Bouwstra, Hans C. Hennies, Ingrid Moll, Matthias Schmuth, Johanna M. Brandner

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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.

Original languageEnglish
Article number2123
Pages (from-to)2777-2789
Number of pages13
JournalAmerican Journal of Pathology
Volume185
Issue number10
Early online date28 Aug 2015
DOIs
Publication statusPublished - Oct 2015
Externally publishedYes

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    Gruber, R., Börnchen, C., Rose, K., Daubmann, A., Volksdorf, T., Wladykowski, E., Vidal-Y-Sy, S., Peters, E. M., Danso, M., Bouwstra, J. A., Hennies, H. C., Moll, I., Schmuth, M., & Brandner, J. M. (2015). Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis. American Journal of Pathology, 185(10), 2777-2789. [2123]. https://doi.org/10.1016/j.ajpath.2015.06.021