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Doctoral thesis
English

Role of the crosstalk between epithelial and mesenchymal cells in fibrotic disorders focusing on IL-25 within systemic sclerosis

ContributorsRusso, Barbara
Defense date2020-04-20
Abstract

Skin fibrosis characterizes systemic sclerosis (SSc). This thesis addresses the question of whether dysfunctional keratinocyte-fibroblast interactions may participate in fibrogenesis and investigates whether epithelial-derived IL-25 may affect skin homeostasis. By using a novel tissue-engineered epidermal-equivalent (EE) generated from SSc and healthy donor (HD) keratinocytes, we found that in vitro SSc-EE reproduces a morphological phenotype characterized by aberrant differentiation and keratinocyte activation mimicking alterations found in vivo. Unbiased transcriptomic analysis showed profound alterations in SSc-EE, including downregulation of homeobox gene expression. Compared to HD, SSc-EE induced enhanced production of inflammatory mediators and matrix metalloproteinases by fibroblasts, but similar production of matrix components. IL-25 enhanced the pro-inflammatory activity of EE and directly inhibited matrix deposition by fibroblasts. The decreased expression of IL-25 in SSc skin suggested that its relative lack could play a role in skin fibrosis. Thèse Results strongly support a role for keratinocytes to modulate matrix turnover amenable to therapeutic intervention.

eng
Citation (ISO format)
RUSSO, Barbara. Role of the crosstalk between epithelial and mesenchymal cells in fibrotic disorders focusing on IL-25 within systemic sclerosis. 2020. doi: 10.13097/archive-ouverte/unige:139015
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Technical informations

Creation07/27/2020 6:16:00 PM
First validation07/27/2020 6:16:00 PM
Update time03/19/2024 3:03:40 PM
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