Moezinia, C.; Wong, V.; Watson, J.; Nagib, L.; Lopez Garces, S.; Zhang, S.; Ahmed Abdi, B.; Newton, F.; Abraham, D.; Stratton, R. Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis. Cells2023, 12, 2490.
Moezinia, C.; Wong, V.; Watson, J.; Nagib, L.; Lopez Garces, S.; Zhang, S.; Ahmed Abdi, B.; Newton, F.; Abraham, D.; Stratton, R. Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis. Cells 2023, 12, 2490.
Moezinia, C.; Wong, V.; Watson, J.; Nagib, L.; Lopez Garces, S.; Zhang, S.; Ahmed Abdi, B.; Newton, F.; Abraham, D.; Stratton, R. Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis. Cells2023, 12, 2490.
Moezinia, C.; Wong, V.; Watson, J.; Nagib, L.; Lopez Garces, S.; Zhang, S.; Ahmed Abdi, B.; Newton, F.; Abraham, D.; Stratton, R. Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis. Cells 2023, 12, 2490.
Abstract
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized 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 evaluation 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 is evaluated for the potential to activate keratinocytes in tissue culture and to induce signaling in TLR2 & 3 reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes, and activation of these cells leading to release of IL-1α, representing a potential initiating pathway in this disease.
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