Dissertation

Human skin equivalents for atopic dermatitis: investigating the role of filaggrin in the skin barrier

Promotor: Prof.dr. J.A. Bouwstra, Co-promotor: Dr. A. El Ghalbzouri

Author: V. van Drongelen
Date: 16 December 2014
Links: Thesis in Leiden Repository

Atopic Dermatitis (AD) is a frequent occurring inflammatory skin disease causing physical discomfort, social embarrassment and stress. This skin disease is characterized by decreased skin barrier function and various other epidermal changes, as well as immunological changes. A decreased skin barrier function allows environmental factors such as allergens and pathogens to penetrate through the skin and evoke an immunological response, which in turn may negatively affect the skin barrier function. The skin barrier is composed of cornified keratinocytes, extracellular lipids and multiple proteins, including filaggrin. The discovery of mutations in the filaggrin gene as a major risk factor for development of AD has intensified research on this protein and its role in AD development, but its exact role in AD is still not clarified. This thesis describes the development of several reconstructed human skin equivalents (HSEs) which recapitulate various characteristics of AD. They display for example reduced filaggrin expression or alterations in epidermal characteristics due to the presence of AD-related inflammatory cytokines. These HSEs are a powerful tool that in the future might be used for screening purposes and/or development of new therapies for this life disabling skin disease.