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Title

Dissecting the Crosstalk between Epithelial and Mesenchymal Cells in the Presence of IL-17A within Systemic Sclerosis
Author
Dufour, Aleksandra Maria
Director
Chizzolini, Carlo
Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. Vie - Bioméd. 4 - 2018/12/14
Abstract Interleukin-17A (IL-17A) is increased in systemic sclerosis (SSc) skin and other organs but its role in disease pathogenesis is debated. Since epithelial cells are preferential targets of IL-17A, we aimed at investigating the role of IL-17A in the interactions between epidermis and dermis in the settings of skin fibrosis. We uncovered an unexpected synergic activity of IL-17A with transforming growth factor-β (TGF-β), the master pro-fibrotic cytokine, resulting in an enhanced production of IL-6 by fibroblasts, driven by p38 MAPK signaling pathway. Simultaneously, we observed a decreased type I collagen production associated with reduced SMAD phosphorylation. In skin explants and in keratinocyte-fibroblast interactions model IL-17A not only decreased extracellular matrix deposition by itself, but also counteracted TGF-β pro-fibrotic activities. These data point to pro-inflammatory and anti-fibrotic properties of IL-17A and may help in directing and interpreting therapeutic approaches in SSc, since IL-17A, TGF-β, and IL-6 are target candidates in clinical trials.
Keywords Interleukin-17A — Systemic sclerosis — Fibrosis — Inflammation — Collagen — MMP-1 — Keratinocytes — Fibroblasts
Identifiers
URN: urn:nbn:ch:unige-1185765
Full text
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Structures
Faculté de médecine / Section de médecine clinique / Département de médecine
Project
Swiss National Science Foundation: ME10205
Citation
(ISO format) 		DUFOUR, Aleksandra Maria. Dissecting the Crosstalk between Epithelial and Mesenchymal Cells in the Presence of IL-17A within Systemic Sclerosis. Université de Genève. Thèse, 2018. doi: 10.13097/archive-ouverte/unige:118576 https://archive-ouverte.unige.ch/unige:118576

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Deposited on : 2019-06-03

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