Minimally-invasive biomarker discovery and functional analyses in Atopic Dermatitis
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and characterized by a great heterogeneity including eczematous lesions, intense pruritus and a chronic or relapsing disease course. Despite increasingly complex and high-quality studies have advanced our understanding of disease pathology and led to the development of accurate targeted therapies, various questions regarding the pathogenesis and the triggering factors contributing to disease manifestation remain unclear. This thesis demonstrates that keratinocytes present one major source of reactive oxygen species (ROS) underlining their substantial contribution to skin inflammation. Pan and specific NADPH oxidase (NOX) inhibition was performed and revealed that inhibition of NOX seems to be effective in lowering oxidative stress and improving survival in AD-model keratinocytes.
Moreover, tape strips, a tool to perform minimally invasive biosampling, obtained from children at high risk for developing AD were used in order to characterize the pro-inflammatory environment in the epidermis. Several pro-inflammatory proteins are highly abundant in the stratum corneum of children at AD onset or even precede disease manifestation. This thesis thereby underlines the feasibility of tape strips for characterization of the inflammatory environment in the skin which would notably improve biosamples quantity required for biomarker identification.
In a third and fourth study, 3-dimensional (3D) models of human skin were applied and refined. T cells and Staphylococcus aureus were incorporated into the 3D skin model to better mimic an in vivo scenario. This resulted in improved model complexity that is essential to conduct functional experiments related to AD pathology.
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