Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis
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Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis. / Gruber, Robert; Börnchen, Christian; Rose, Katharina ; Daubmann, Anne; Volksdorf, Thomas; Wladykowski, Ewa; Vidal-Y-Sy, Sabine; Peters, Eva M; Danso, Mogbekeloluwa; Bouwstra, Joke A; Hennies, Hans C; Moll, Ingrid; Schmuth, Matthias; Brandner, Johanna M.
In: AM J PATHOL, Vol. 185, No. 10, 10.2015, p. 2777-89.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis
AU - Gruber, Robert
AU - Börnchen, Christian
AU - Rose, Katharina
AU - Daubmann, Anne
AU - Volksdorf, Thomas
AU - Wladykowski, Ewa
AU - Vidal-Y-Sy, Sabine
AU - Peters, Eva M
AU - Danso, Mogbekeloluwa
AU - Bouwstra, Joke A
AU - Hennies, Hans C
AU - Moll, Ingrid
AU - Schmuth, Matthias
AU - Brandner, Johanna M
N1 - Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PY - 2015/10
Y1 - 2015/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.ajpath.2015.06.021
DO - 10.1016/j.ajpath.2015.06.021
M3 - SCORING: Journal article
C2 - 26319240
VL - 185
SP - 2777
EP - 2789
JO - AM J PATHOL
JF - AM J PATHOL
SN - 0002-9440
IS - 10
ER -
