ArticleFrontiers in immunology2023
GM-CSF-activated STAT5A regulates macrophage functions and inflammation in atherosclerosis.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- Modulation of immune responses by elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis: data from a compassionate use program.Respiratory research · 2026Article
- Thrombotic thrombocytopenic purpura and macrophage activation syndrome secondary to Sjögren's syndrome: a case report.Frontiers in immunology · 2026Article
- Targeting the Th17/Treg axis: from immunological insights to therapeutic avenues in atherosclerosis.Frontiers in immunology · 2026Review
- Targeting GM-CSF in Rheumatoid Arthritis: Advances in Cytokine-Directed Immunotherapy and Clinical Implications.Life (Basel, Switzerland) · 2025Review
- STK11 coordinates IL-4 signaling with metabolic reprogramming to control M2 macrophage polarization and antitumor immunity.Science advances · 2025Article
- Neuregulin 4 inhibits synovial macrophage pro-inflammatory polarization via ErbB4/Stat5b/NF-κB signaling to alleviate osteoarthritis progression.Journal of orthopaedic surgery and research · 2025Article
- Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis.Science advances · 2025Article
- GM-CSF potentiates macrophages to retain an inflammatory feature from their circulating monocyte precursors in rheumatoid arthritis.Journal of translational medicine · 2025Article
- Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.Clinical epigenetics · 2025Article
- Omega-3 fatty acid synergy with glucocorticoid in mouse lupus macrophage model: targeting pathogenic pathways to reduce steroid dependence.Frontiers in immunology · 2025Article
- Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.Journal for immunotherapy of cancer · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Inhibition of STAT5 was recently reported to reduce murine atherosclerosis. However, the role of STAT5 isoforms, and more in particular STAT5A in macrophages in the context of human atherosclerosis remains unknown. Methods and results: Here, we demonstrate reciprocal expression regulation of STAT5A and STAT5B in human atherosclerotic lesions. The former was highly upregulated in ruptured over stable plaque and correlated with macrophage presence, a finding that was corroborated by the high chromosomal accessibility of STAT5A but not B gene in plaque macrophages. Phosphorylated STAT5 correlated with macrophages confirming its activation status. As macrophage STAT5 is activated by GM-CSF, we studied the effects of its silencing in GM-CSF differentiated human macrophages. STAT5A knockdown blunted the immune response, phagocytosis, cholesterol metabolism, and augmented apoptosis terms on transcriptional levels. These changes could partially be confirmed at functional level, with significant increases in apoptosis and decreases in lipid uptake and IL-6, IL-8, and TNFa cytokine secretion after STAT5A knockdown. Finally, inhibition of general and isoform A specific STAT5 significantly reduced the secretion of TNFa, IL-8 and IL-10 in ex vivo tissue slices of advanced human atherosclerotic plaques. Discussion: In summary, we identify STAT5A as an important determinant of macrophage functions and inflammation in the context of atherosclerosis and show its promise as therapeutic target in human atherosclerotic plaque inflammation.
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