Macrophages as determinants and regulators of fibrosis in systemic sclerosis. (21st July 2022)

• Record Type: Journal Article
• Authors: Al-Adwi, Yehya; Westra, Johanna; van Goor, Harry; Burgess, Janette K; Denton, Christopher P; Mulder, Douwe J
• Is Part Of: Rheumatology. Volume 62:Number 2(2023)
• Page Start: 535
• Page End: 545
• Publication Date: 2022-07-21
• Subjects: scleroderma -- SSc -- macrophages -- monocytes -- fibrosis -- potential targeted therapeutics; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keac410
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: 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. Graphical Abstract: