Beyond very early systemic sclerosis: deciphering pre‑scleroderma and its trajectories to open new avenues for preventive medicine

Lescoat, Alain; Bellando-Randone, Silvia; Campochiaro, Corrado; Del Galdo, Francesco; Denton, Christopher P; Farrington, Sue; Galetti, Ilaria; Khanna, Dinesh; Kuwana, Masataka; Truchetet, Marie-Elise; Allanore, Yannick; Matucci-Cerinic, Marco

doi:10.1016/s2665-9913(23)00212-6

Cited by 6 publications

(1 citation statement)

References 84 publications

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“…It is thought that an initial insult such as viral infection or exposure to toxins, triggers endothelial cell activation, initiating the disease in genetically susceptible individuals. This, coupled to autoantibody driven endothelial cell dysfunction, leads to a vascular profile characteristic of limited systemic sclerosis or in some patients triggering an early inflammatory profile which can progress towards diffuse cutaneous system sclerosis [44]. Endothelial cell apoptosis and altered expression of adhesion molecules and cytokines might lead to the release of reactive oxygen species (ROS), resulting in continuous microvessel damage [45].…”

Section: Vasculopathymentioning

confidence: 99%

Role of Macrophages in Promoting Inflammation and Fibrosis in Systemic Sclerosis

Lopez Garces,

Pan,

Stratton

2024

Macrophages - Molecular Pathways and Immunometabolic Processes [Working Title]

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Systemic sclerosis (SSc) is a severe autoimmune disease characterized by chronic inflammation, vascular damage and fibrosis. The hallmark clinical manifestation is fibrotic skin thickening; however, the clinical outcome is determined by the extent of internal organ fibrosis. Macrophages, integral to the innate immune system, play a crucial role in phagocytosing invading pathogens and efferocytosis of apoptotic cells, while also contributing significantly to tissue homeostasis and repair. These highly adaptable cells, particularly in the M2-like polarization state, have been associated with a pro-fibrotic environment, implicated in various fibrotic disorders as well as cancer invasion. In SSc, these cells may be dysfunctional, having the potential to produce inflammatory and pro-fibrotic cytokines, recruit other inflammatory cells and stimulate fibroblast differentiation into myofibroblast, thus promoting extracellular matrix (ECM) deposition and fibrosis. Accordingly, we hypothesize that abnormally activated macrophages have a central role in SSc, promoting inflammation and fibrosis, and driving the disease process.

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Section: Vasculopathymentioning

confidence: 99%