GM-CSF potentiates macrophages to retain an inflammatory feature from their circulating monocyte precursors in rheumatoid arthritis

作者：Jianing Chen, Minghua Zhan, Yanling Zhao, Honglin Xu, Futai Feng, Zhou Bai, Ke Zhang, Longlong Fu, Fang Wang, Yongjing Cheng, Xuan Zhang, Yudong Liu · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06911-7 · 被引用次数：8 · 研究领域：Immune cells in cancer、Rheumatoid Arthritis Research and Therapies、Chemokine receptors and signaling

Peripheral monocytes represent an important source of macrophages in the synovium of rheumatoid arthritis (RA). However, it remains unclear whether the proinflammatory traits in RA monocytes can be maintained during their differentiation into macrophages without exogenous polarization stimuli. Peripheral blood CD14 + monocytes from RA patients and healthy controls (HCs) were differentiated into macrophages in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). Transcriptomic analysis, metabolic profiling, flow cytometry, and functional assays were performed. Transcriptomic and functional analyses revealed that GM-CSF-differentiated macrophages (GM-DMs) from RA monocytes preserved a proinflammatory M1-like phenotype, whereas M-CSF-differentiated macrophages (M-DMs) lost this phenotype. Synovial GM-CSF expression levels were significantly elevated in RA patients compared to HCs and were positively correlated with disease activity (DAS28-CRP). In contrast, M-CSF expression levels were reduced and inversely correlated with DAS28-CRP. RA GM-DMs exhibited hyperactivation of the STAT5 signaling and a hypermetabolic profile, characterized by enhanced oxidative phosphorylation (OXPHOS) and impaired glycolysis. Strikingly, CCL22 was identified as the most upregulated chemokine in RA GM-DMs. Elevated synovial CCL22 expression strongly correlated with M1 macrophage infiltration and disease activity. Functionally, CCL2...