TY - JOUR VL - 12 UR - https://doi.org/10.3390/cells12202490 A1 - Moezinia, Carine A1 - Wong, Valerie A1 - Watson, James A1 - Nagib, Lydia A1 - Lopez Garces, Sandra A1 - Zhang, Siyu A1 - Ahmed Abdi, Bahja A1 - Newton, Florence A1 - Abraham, David A1 - Stratton, Richard AV - public N2 - 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-1?, representing a potential initiating pathway in this disease. JF - Cells KW - scleroderma; autoantibody; epithelial cell; fibrosis ID - discovery10179789 IS - 20 PB - MDPI AG N1 - © 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/). TI - Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis Y1 - 2023/10/20/ SN - 2073-4409 ER -