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Macrophages as determinants and regulators of fibrosis in systemic sclerosis

Al-Adwi, Yehya; Westra, Johanna; Van Goor, Harry; Burgess, Janette K; Denton, Christopher P; Mulder, Douwe J; (2022) Macrophages as determinants and regulators of fibrosis in systemic sclerosis. Rheumatology 10.1093/rheumatology/keac410. (In press). Green open access

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Abstract

Systemic Sclerosis (SSc) is a multiphase autoimmune disease with a well-known triad of clinical manifestations including vasculopathy, inflammation and fibrosis. Although a plethora of drugs has been suggested as potential candidates to halt SSc progression, nothing has proven clinically efficient. In SSc, both innate and adaptive immune systems are abnormally activated fuelling fibrosis of the skin and other vital organs. Macrophages have been implicated in the pathogenesis of SSc and are thought to be a major source of immune dysregulation. Due to their plasticity, macrophages can initiate and sustain chronic inflammation when classically activated while, simultaneously or parallelly, when alternatively activated they are also capable of secreting fibrotic factors. Here, we briefly explain the polarization process of macrophages. Subsequently, we link the activation of macrophages and monocytes to the molecular pathology of SSc, and illustrate the interplay between macrophages and fibroblasts. Finally, we present recent/near-future clinical trials and discuss novel targets related to macrophages/monocytes activation in SSc.

Type: Article
Title: Macrophages as determinants and regulators of fibrosis in systemic sclerosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keac410
Publisher version: https://doi.org/10.1093/rheumatology/keac410
Language: English
Additional information: Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
Keywords: fibrosis, macrophages, monocytes, potential targeted therapeutics, scleroderma, systemic sclerosis
UCL classification: 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 > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10152686
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