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Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization
by
Yang, Jin
, Lu, Yulei
, Wang, Jianfang
, Cai, Zhejun
, Lu, Chengjie
, Wang, Yidong
, Shu, Qiang
, Ru, Wei
, Wei, Jia
, Lu, Yi
, Jia, Liangliang
, Tang, Daxing
in
Allergology
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - genetics
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ CCL4 protein
/ Chromatin
/ Disease Models, Animal
/ Disease Susceptibility
/ Enterocolitis, Necrotizing - etiology
/ Enterocolitis, Necrotizing - metabolism
/ Enterocolitis, Necrotizing - pathology
/ Enterocolitis, Necrotizing - prevention & control
/ Epithelial cells
/ Fluorescent Antibody Technique
/ Gastroenterology
/ Gastrointestinal diseases
/ Humans
/ Immunohistochemistry
/ Immunology
/ Immunoprecipitation
/ Infant, Newborn
/ Inflammatory diseases
/ Interferon
/ Interferon regulatory factor
/ Interferon Regulatory Factors - deficiency
/ Interleukin 1
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Macrophage Activation - genetics
/ Macrophage Activation - immunology
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Transgenic
/ Myeloid cells
/ Myeloid Cells - immunology
/ Myeloid Cells - metabolism
/ Necrosis
/ Necrotizing enterocolitis
/ Neonates
/ Pathogenesis
/ Phenotypes
/ Polarization
/ Severity of Illness Index
/ Tumor necrosis factor
2019
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Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization
by
Yang, Jin
, Lu, Yulei
, Wang, Jianfang
, Cai, Zhejun
, Lu, Chengjie
, Wang, Yidong
, Shu, Qiang
, Ru, Wei
, Wei, Jia
, Lu, Yi
, Jia, Liangliang
, Tang, Daxing
in
Allergology
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - genetics
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ CCL4 protein
/ Chromatin
/ Disease Models, Animal
/ Disease Susceptibility
/ Enterocolitis, Necrotizing - etiology
/ Enterocolitis, Necrotizing - metabolism
/ Enterocolitis, Necrotizing - pathology
/ Enterocolitis, Necrotizing - prevention & control
/ Epithelial cells
/ Fluorescent Antibody Technique
/ Gastroenterology
/ Gastrointestinal diseases
/ Humans
/ Immunohistochemistry
/ Immunology
/ Immunoprecipitation
/ Infant, Newborn
/ Inflammatory diseases
/ Interferon
/ Interferon regulatory factor
/ Interferon Regulatory Factors - deficiency
/ Interleukin 1
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Macrophage Activation - genetics
/ Macrophage Activation - immunology
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Transgenic
/ Myeloid cells
/ Myeloid Cells - immunology
/ Myeloid Cells - metabolism
/ Necrosis
/ Necrotizing enterocolitis
/ Neonates
/ Pathogenesis
/ Phenotypes
/ Polarization
/ Severity of Illness Index
/ Tumor necrosis factor
2019
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Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization
by
Yang, Jin
, Lu, Yulei
, Wang, Jianfang
, Cai, Zhejun
, Lu, Chengjie
, Wang, Yidong
, Shu, Qiang
, Ru, Wei
, Wei, Jia
, Lu, Yi
, Jia, Liangliang
, Tang, Daxing
in
Allergology
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - genetics
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ CCL4 protein
/ Chromatin
/ Disease Models, Animal
/ Disease Susceptibility
/ Enterocolitis, Necrotizing - etiology
/ Enterocolitis, Necrotizing - metabolism
/ Enterocolitis, Necrotizing - pathology
/ Enterocolitis, Necrotizing - prevention & control
/ Epithelial cells
/ Fluorescent Antibody Technique
/ Gastroenterology
/ Gastrointestinal diseases
/ Humans
/ Immunohistochemistry
/ Immunology
/ Immunoprecipitation
/ Infant, Newborn
/ Inflammatory diseases
/ Interferon
/ Interferon regulatory factor
/ Interferon Regulatory Factors - deficiency
/ Interleukin 1
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Macrophage Activation - genetics
/ Macrophage Activation - immunology
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Mice
/ Mice, Transgenic
/ Myeloid cells
/ Myeloid Cells - immunology
/ Myeloid Cells - metabolism
/ Necrosis
/ Necrotizing enterocolitis
/ Neonates
/ Pathogenesis
/ Phenotypes
/ Polarization
/ Severity of Illness Index
/ Tumor necrosis factor
2019
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Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization
Journal Article
Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization
2019
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Overview
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.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited
Subject
/ Animals
/ Biomedical and Life Sciences
/ Biopsy
/ Enterocolitis, Necrotizing - etiology
/ Enterocolitis, Necrotizing - metabolism
/ Enterocolitis, Necrotizing - pathology
/ Enterocolitis, Necrotizing - prevention & control
/ Fluorescent Antibody Technique
/ Humans
/ Interferon regulatory factor
/ Interferon Regulatory Factors - deficiency
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Macrophage Activation - genetics
/ Macrophage Activation - immunology
/ Mice
/ Necrosis
/ Neonates
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