ArticleMucosal immunology2019
Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization.
Article in Mucosal immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- The role of IRF5 as an immune regulator.Biochemical Society transactions · 2026Review
- ROS-Dependent GSDMD Activation Drives Intestinal Pyroptosis in Neonatal Necrotizing Enterocolitis (NEC).Cell biology international · 2026Article
- TOPK Suppresses the CD8Cancer communications (London, England) · 2026Article
- GSDMD deficiency attenuates BPD by suppressing macrophage pyroptosis and promoting M2 polarization.Cell death discovery · 2025Article
- A Potentially TREMendous Treatment: TREM1 Inhibition as a Novel Therapy for Necrotizing Enterocolitis.Digestive diseases and sciences · 2025Article
- Targeting TREM1 Ameliorates Necrotizing Enterocolitis in Neonatal Mice by Inhibiting Endoplasmic Reticulum Stress and Regulating Macrophage Polarization.Digestive diseases and sciences · 2025Article
- Immunological characteristics and functions of macrophages in Mycobacterium leprae infection.BMC immunology · 2025Article
- GSDMD deficiency mitigates intestinal damage via macrophage pyroptosis control in experimental NEC.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Inhibition of ferroptosis in inflammatory macrophages alleviates intestinal injury in neonatal necrotizing enterocolitis.Cell death discovery · 2025Article
- Spatial transcriptomics delineates potential differences in intestinal phenotypes of cardiac and classical necrotizing enterocolitis.iScience · 2025Article
- The role of natural products targeting macrophage polarization in sepsis-induced lung injury.Chinese medicine · 2025Review
- Multi-Omics Analysis of Aberrances and Functional Implications of IRF5 in Digestive Tract Tumours.Journal of cellular and molecular medicine · 2025Article
- Neuroimmune Crossroads: The Interplay of the Enteric Nervous System and Intestinal Macrophages in Gut Homeostasis and Disease.Biomolecules · 2024Review
- IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.JCI insight · 2024Article
- CCL3 aggravates intestinal damage in NEC by promoting macrophage chemotaxis and M1 macrophage polarization.Pediatric research · 2023Article
- An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.Nature communications · 2023Article
- New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.Frontiers in immunology · 2023Review
- Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role ofiScience · 2022Article
- Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.Genes & diseases · 2022Review
- Ccl3 enhances docetaxel chemosensitivity in breast cancer by triggering proinflammatory macrophage polarization.Journal for immunotherapy of cancer · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease in newborns, but the mechanisms remain unclear. Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage function and is essential for proinflammatory M1 macrophage polarization. Our previous data indicated that M1 macrophages promote NEC injury. Here, we investigated whether IRF5 is involved in the pathogenesis of NEC. First, we found that IRF5 was upregulated in infiltrated macrophages in human neonates with NEC compared to controls. We further confirmed IRF5 upregulation in macrophages in experimental murine NEC and that the infiltrated macrophages were predominantly polarized into the M1 but not the M2 phenotype. Myeloid-specific deficiency of Irf5, which was associated with reduced M1 macrophage polarization and systematic inflammation, dramatically prevented experimental NEC. Moreover, we found that the ablation of Irf5 in myeloid cells markedly suppressed intestinal epithelial cell apoptosis and further prevented intestinal barrier dysfunction in experimental NEC. Bioinformatic and chromatin immunoprecipitation analysis further showed that IRF5 binds to the promoters of the M1 macrophage-associated genes Ccl4, Ccl5, Tnf, and Il12b. Overall, our study provides evidence that IRF5 participates in the pathogenesis of NEC, while the deletion of Irf5 in myeloid cells prevents NEC via inhibiting M1 macrophage polarization.
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