BPIFA1 Regulates Interferon-Mediated Lung Neutrophil Recruitment During Acute Inflammation
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PROVIDER: PRJNA412049 | ENA |
REPOSITORIES: ENA
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Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was “cell movement” including E-selectin, which was coordinately regulated with IL-1. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1, which together with IFN-, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease. 6 ENL skin lesions and 7 Lepromatous leprosy skin lesions
2009-06-30 | E-GEOD-16844 | biostudies-arrayexpress
Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was 'cell movement' including E-selectin, which was coordinately regulated with IL-1beta. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1beta, which together with IFN-gamma, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.
2009-06-30 | GSE16844 | GEO
Project description:BPIFA1 (BPI-fold containing group A member 1) is an airway host-protective protein with immunomodulatory properties that binds to LPS and is regulated by infectious and inflammatory signals. Differential expression of BPIFA1 has been widely reported in lung disease, yet the biological significance of this observation is unclear. We sought to understand the role of BPIFA1 fluctuations in modulating lung inflammation. We treated WT and bpifa1-/- mice with intranasal LPS and performed transcriptomic analyses to determine the immune effects of BPIFA1 deficiency. Transcriptomic analysis revealed a signature of 379 genes that differentiated bpifa1-/- mice from WT. During acute lung inflammation, the most strongly downregulated innate immunity genes in bpifa1-/- mice were cxcl9 and cxcl10. This was consistent with significantly decreased expression of IFN-g, IFN-l and downstream IFN-stimulated genes (ISG) and IFN-regulatory factors (IRF) important for innate immune responses.
2017-09-26 | GSE104214 | GEO
Project description:Mouse neutrophil maturity analysis in homeostasis, acute-inflammation and cancer
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Project description:Tissue repair requires the resolution of inflammation. However, the molecular mechanisms that attenuate inflammation in vivo are not fully understood. Here, we identify that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive tissue repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as a key feature of macrophages during inflammatory resolution. Dietary depletion studies and conditional deletion of glutaminase (Gls), the essential enzyme involved in glutamine metabolism, in innate immune cells in mice reveals an essential role for glutamine metabolism in suppressing inflammation and promoting tissue repair. Genes involved in neutrophil recruitment are upregulated in macrophages lacking Gls and in foot ulcers of diabetic patients. Multimodal single cell transcriptomics and epigenomics reveals that Gls is required for chromatin remodeling of neutrophil recruitment genes in innate immune cells during resolution of inflammation. These findings highlight the role of glutamine metabolism in controlling cellular communication during tissue repair and suppressing neutrophil recruitment to advance inflammation resolution.
2026-02-01 | GSE289255 | GEO
Project description:Tissue repair requires the resolution of inflammation. However, the molecular mechanisms that attenuate inflammation in vivo are not fully understood. Here, we identify that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive tissue repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as a key feature of macrophages during inflammatory resolution. Dietary depletion studies and conditional deletion of glutaminase (Gls), the essential enzyme involved in glutamine metabolism, in innate immune cells in mice reveals an essential role for glutamine metabolism in suppressing inflammation and promoting tissue repair. Genes involved in neutrophil recruitment are upregulated in macrophages lacking Gls and in foot ulcers of diabetic patients. Multimodal single cell transcriptomics and epigenomics reveals that Gls is required for chromatin remodeling of neutrophil recruitment genes in innate immune cells during resolution of inflammation. These findings highlight the role of glutamine metabolism in controlling cellular communication during tissue repair and suppressing neutrophil recruitment to advance inflammation resolution.
2026-02-01 | GSE289254 | GEO
Project description:Bpifa1 (BPI fold-containing group A member 1) is an airway host-protective protein with immunomodulatory properties that binds to LPS and is regulated by infectious and inflammatory signals. Differential expression of Bpifa1 has been widely reported in lung disease, yet the biological significance of this observation is unclear. We sought to understand the role of Bpifa1 fluctuations in modulating lung inflammation. We treated wild-type (WT) and Bpifa1-/- mice with intranasal LPS and performed immunological and transcriptomic analyses of lung tissue to determine the immune effects of Bpifa1 deficiency. We show that neutrophil (polymorphonuclear cells, PMNs) lung recruitment and transmigration to the airways in response to LPS is impaired in Bpifa1-/- mice. Transcriptomic analysis revealed a signature of 379 genes that differentiated Bpifa1-/- from WT mice. During acute lung inflammation, the most downregulated genes in Bpifa1-/- mice were Cxcl9 and Cxcl10. Bpifa1-/- mice had lower bronchoalveolar lavage concentrations of C-X-C motif chemokine ligand 10 (Cxcl10) and Cxcl9, interferon-inducible PMN chemokines. This was consistent with lower expression of IFNγ, IFNλ, downstream IFN-stimulated genes, and IFN-regulatory factors, which are important for the innate immune response. Administration of Cxcl10 before LPS treatment restored the inflammatory response in Bpifa1-/- mice. Our results identify a novel role for Bpifa1 in the regulation of Cxcl10-mediated PMN recruitment to the lungs via IFNγ and -λ signaling during acute inflammation.
| S-EPMC6397348 | biostudies-literature
Project description:Tissue repair requires the resolution of inflammation. However, the molecular mechanisms that attenuate inflammation in vivo are not fully understood. Here, we identify that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive tissue repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as a key feature of macrophages during inflammatory resolution. Dietary depletion studies and conditional deletion of glutaminase (Gls), the essential enzyme involved in glutamine metabolism, in innate immune cells in mice reveals an essential role for glutamine metabolism in suppressing inflammation and promoting tissue repair. Genes involved in neutrophil recruitment are upregulated in macrophages lacking Gls and in foot ulcers of diabetic patients. Multimodal single cell transcriptomics and epigenomics reveals that Gls is required for chromatin remodeling of neutrophil recruitment genes in innate immune cells during resolution of inflammation. These findings highlight the role of glutamine metabolism in controlling cellular communication during tissue repair and suppressing neutrophil recruitment to advance inflammation resolution.
2026-02-01 | GSE289200 | GEO
Project description:Tissue repair requires the resolution of inflammation. However, the molecular mechanisms that attenuate inflammation in vivo are not fully understood. Here, we identify that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive tissue repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as a key feature of macrophages during inflammatory resolution. Dietary depletion studies and conditional deletion of glutaminase (Gls), the essential enzyme involved in glutamine metabolism, in innate immune cells in mice reveals an essential role for glutamine metabolism in suppressing inflammation and promoting tissue repair. Genes involved in neutrophil recruitment are upregulated in macrophages lacking Gls and in foot ulcers of diabetic patients. Multimodal single cell transcriptomics and epigenomics reveals that Gls is required for chromatin remodeling of neutrophil recruitment genes in innate immune cells during resolution of inflammation. These findings highlight the role of glutamine metabolism in controlling cellular communication during tissue repair and suppressing neutrophil recruitment to advance inflammation resolution.
2026-02-01 | GSE289135 | GEO
Project description:Positionally distinct interferon-stimulated dermal immune-acting fibroblasts promote neutrophil recruitment in Sweet's syndrome.
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