[HTML][HTML] Type 2 helper T-cell cytokines induce morphologic and molecular characteristics of atopic dermatitis in human skin equivalent

M Kamsteeg, M Bergers, R de Boer… - The American journal of …, 2011 - Elsevier
M Kamsteeg, M Bergers, R de Boer, PLJM Zeeuwen, SV Hato, J Schalkwijk, GS Tjabringa
The American journal of pathology, 2011Elsevier
Both the immune system and the epidermis likely have an important role in the pathogenesis
of atopic dermatitis (AD). The objective of the present study was to develop a human skin
equivalent model exhibiting morphologic and molecular characteristics of AD in a controlled
manner. Skin equivalents generated from normal adult human keratinocytes were stimulated
with type 2 T-helper cell (Th2) cytokines IL-4 and IL-13, and morphologic features and gene
expression of the epidermis were studied. Th2 cytokines induced intercellular edema similar …
Both the immune system and the epidermis likely have an important role in the pathogenesis of atopic dermatitis (AD). The objective of the present study was to develop a human skin equivalent model exhibiting morphologic and molecular characteristics of AD in a controlled manner. Skin equivalents generated from normal adult human keratinocytes were stimulated with type 2 T-helper cell (Th2) cytokines IL-4 and IL-13, and morphologic features and gene expression of the epidermis were studied. Th2 cytokines induced intercellular edema similar to spongiotic changes observed in lesional AD as assessed at histopathologic analysis and electron microscopy. Furthermore, genes known to be specifically expressed in epidermis of patients with AD such as CAII and NELL2 were induced. In contrast, expression of psoriasis-associated genes such as elafin and hBD2 was not changed. Th2 cytokines caused DNA fragmentation in the keratinocytes, which could be inhibited by the caspase inhibitor Z-VAD, which suggests that apoptosis was induced. In addition, up-regulation of the death receptor Fas was observed in keratinocytes after Th2 cytokine stimulation. IL-4 and IL-13 induced phosphorylation of the signaling molecule STAT6. It was concluded that the skin equivalent model described herein may be useful in investigation of the epidermal aspects of AD and for study of drugs that act at the level of keratinocyte biology.
Elsevier