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

作者：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; Brandner Johanna M^*

来源：American Journal Of Pathology, 2015, 185(10): 2777-2789.

DOI：10.1016/j.ajpath.2015.06.021

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.

• 出版日期2015-10