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Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis

Moezinia, Carine; Wong, Valerie; Watson, James; Nagib, Lydia; Lopez Garces, Sandra; Zhang, Siyu; Ahmed Abdi, Bahja; ... Stratton, Richard; + view all (2023) Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis. Cells , 12 (20) , Article 2490. 10.3390/cells12202490. Green open access

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Abstract

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by pathological processes involving autoimmunity, vasculopathy and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper, we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluate the binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera was evaluated for the potential to activate keratinocytes in tissue culture and to induce TLR2 and 3 signalling in reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes and the activation of these cells leading to the release of IL-1α, representing a potential initiating pathway in this disease.

Type: Article
Title: Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/cells12202490
Publisher version: https://doi.org/10.3390/cells12202490
Language: English
Additional information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: scleroderma; autoantibody; epithelial cell; fibrosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10179789
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