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The following is a summary of “Elevated Fcy receptor expression augments pro-inflammatory macrophage phagocytosis in systemic sclerosis and associated rheumatic diseases,” published in the December 2024 issue of Rheumatology by Hukara et al.
Researchers conducted a retrospective study to explore the pro-phagocytic phenotype of macrophages in SSc and other rheumatic diseases, focusing on activation, signaling pathways, and treatment responses driving enhanced phagocytosis.
They analyzed scRNA-seq datasets (GSE138669/GSE212109) from skin and lung macrophages of healthy controls and patients with systemic sclerosis (SSc). Human monocyte-derived macrophages (hMDM) were differentiated from CD14+ monocytes of healthy controls, patients with SSc, RA, PsA, and axSpA. In some experiments hMDMs pretreated with 0.1 μM nintedanib. Phagocytosis was measured using pHrodo bioparticles and flow cytometry, while surface markers, NF-κB signaling, and gene expression were assessed by flow cytometry, Western blot, and RT-qPCR, respectively.
The results showed a pro-phagocytic signature in SSc-affected organs. SSc macrophages, particularly the FCGR3Ahi cluster in skin, had elevated FCGR gene expression and enriched FcγR-mediated phagocytosis pathways with pro-inflammatory markers. This phenotype extended to FCN1hi lung macrophages in patients suffering from SSc with interstitial lung disease. hMDMs from patients with SSc, RA, and PsA exhibited enhanced phagocytic activity. Elevated FcγRI and FcγRII levels drove increased phagocytosis and IL-6-driven inflammation. Nintedanib reduced FcγRI expression, suggesting potential therapeutic benefit in attenuating phagocytosis.
Investigators highlighted FcγR-expressing macrophages as key drivers of phagocytosis and inflammation in SSc. Dysregulated activation of these macrophages contributed to persistent inflammation and fibrosis, suggesting new therapeutic approaches.
Source: academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae688/7923431
