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Extracellular matrix remodeling in atopic dermatitis harnesses the onset of an asthmatic phenotype and is a potential contributor to the atopic march

Item Type:Article
Title:Extracellular matrix remodeling in atopic dermatitis harnesses the onset of an asthmatic phenotype and is a potential contributor to the atopic march
Creators Name:Graff, P. and Woerz, D. and Wilzopolski, J. and Voss, A. and Sarrazin, J. and Blimkie, T.M. and Weiner, J. and Kershaw, O. and Panwar, P. and Hackett, T. and Lau, S. and Brömme, D. and Beule, D. and Lee, Y.A. and Hancock, R.E.W. and Gruber, A.D. and Bäumer, W. and Hedtrich, S.
Abstract:The development of atopic dermatitis (AD) in infancy, and subsequent allergies such as asthma in later childhood, is known as the atopic march. The mechanism is largely unknown, yet the course of disease indicates an inter-epithelial crosstalk, through the onset of inflammation in the skin and progression to another mucosal epithelium. Here, we investigated if and how skin-lung epithelial crosstalk contributes to the development of the atopic march. First, we emulated inter-epithelial crosstalk through indirect co-culture of bioengineered atopic-like skin disease models and three-dimensional bronchial epithelial models triggering an asthma-like phenotype in the latter. A subsequent secretome analysis identified thrombospondin-1, CD44, complement factor C3, fibronectin, and syndecan-4 as potentially relevant skin-derived mediators. As these mediators are extracellular matrix (ECM)-related proteins, we then studied the involvement of the ECM, unveiling distinct proteomic, transcriptomic, and ultrastructural differences in atopic samples. The latter indicated ECM remodeling triggering the release of the above-mentioned mediators. In vivo mouse data showed that exposure to these mediators dysregulated activated circadian clock genes which are increasingly discussed in the context of atopic diseases and asthma development. Our data point toward the existence of a skin-lung axis that could contribute to the atopic march driven by skin ECM remodeling.
Source:Journal of Investigative Dermatology
ISSN:0022-202X
Publisher:Elsevier
Date:13 October 2023
Official Publication:https://doi.org/10.1016/j.jid.2023.09.278
PubMed:View item in PubMed

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