Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutrophil-induced lipoxygenase subtype promotes resolution of acute lung injury in mice

ABSTRACT: Neutrophils are first responders to injury, playing a crucial role in mediating early inflammation. Recently, additional roles for neutrophils have been postulated in tissue repair and resolution of inflammation. Here, we identified a distinct subset of SiglecF+ neutrophils that emerged during mouse lung injury resolution that expressed 12/15-lipoxygenase. These SiglecF+ neutrophils demonstrated distinct anatomic distribution, morphology, gene expression and cell function compared to eosinophils and other neutrophil subsets. Notably, SiglecF+ neutrophils produced specialized pro-resolving mediators (SPMs) and macrophage colony-stimulating factor (M-CSF) that promoted monocyte differentiation into keratinocyte growth factor expressing-macrophages. Depletion of neutrophils hindered alveolar epithelial cell type II (AT2) repair, while adoptive transfer of SiglecF+ neutrophils accelerated epithelial restitution. Furthermore, TGF-b and GM-CSF, acting via AP-1/Jun, promoted SiglecF and 12/15-lipoxygenase expression in mouse neutrophils, and 15-lipoxygenase-1 in human neutrophils. Frequency of BAL 15-lipoxygenase+ neutrophils positively correlated with PaO2/FiO2 in ICU patients. Administration of 15-lipoxygenase-derived SPMs accelerated injury resolution and repair. Together, these findings uncover a pro-resolving subtype of neutrophils that play a pivotal role in the resolution of tissue injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE309959 | GEO | 2025/12/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neutrophil-induced lipoxygenase subtype promotes resolution of acute lung injury in mice (human version)

Project description:Neutrophils are first responders to injury, playing a crucial role in mediating early inflammation. Recently, additional roles for neutrophils have been postulated in tissue repair and resolution of inflammation. Here, we identified a distinct subset of SiglecF+ neutrophils that emerged during mouse lung injury resolution that expressed 12/15-lipoxygenase. These SiglecF+ neutrophils demonstrated distinct anatomic distribution, morphology, gene expression and cell function compared to eosinophils and other neutrophil subsets. Notably, SiglecF+ neutrophils produced specialized pro-resolving mediators (SPMs) and macrophage colony-stimulating factor (M-CSF) that promoted monocyte differentiation into keratinocyte growth factor expressing-macrophages. Depletion of neutrophils hindered alveolar epithelial cell type II (AT2) repair, while adoptive transfer of SiglecF+ neutrophils accelerated epithelial restitution. Furthermore, TGF-b and GM-CSF, acting via AP-1/Jun, promoted SiglecF and 12/15-lipoxygenase expression in mouse neutrophils, and 15-lipoxygenase-1 in human neutrophils. Frequency of BAL 15-lipoxygenase+ neutrophils positively correlated with PaO2/FiO2 in ICU patients. Administration of 15-lipoxygenase-derived SPMs accelerated injury resolution and repair. Together, these findings uncover a pro-resolving subtype of neutrophils that play a pivotal role in the resolution of tissue injury.

2025-12-23 | GSE310118 | GEO

RNA-sequencing of regenerating planaria Dugesia japonica

Project description:We employed RNA-sequencing with surgically resected planaria and cysteinyl-specialized pro-resolving mediators (cys-SPMs), including MCTR3, PCTR3 and RCTR3 to identify genes and pathways activated by cys-SPMs.

2021-03-01 | GSE160278 | GEO

Immunoresolving lipid mediators support effective skeletal muscle repair

Project description:Specialized pro-resolving mediators (SPMs) function to limit inflammation and actively stimulate

2020-03-12 | GSE146785 | GEO

Investigating the role of aging and lung fibrosis in Endothelial Cells with RNA sequencing

Project description:In order to elucidate the contribute of the pulmonary vasculature to lung fibrosis, we injured young and aged mice with bleomycine, to create a model of resolving versus persistent lung fibrosis. The animals were sacrificed 30 days after the injury (time point in which we observed a divergent resolving vs persistent lung fibrosis in young vs aged mice). We found that lung fibrosis resolution in young mice was accompained by the activation of transcriptional programs promoting vascular repair and lung fibrosis resolution. Lung endothelial cells from aged mice after injury failed to activate these programs, leading to dysrepair and progressive fibrosis.

2021-09-30 | GSE181508 | GEO

Proteomic analysis reveals a protective role of specific macrophage subsets in liver repair

Project description:Macrophages are a heterogeneous population of immune cells that play central roles in a broad range of biological processes, including the resolution of inflammation. Although diverse macrophage subpopulations have been identified, the characterization and functional specialization of certain macrophage subsets in inflamed tissues remain unclear. Here we uncovered a key role of specific macrophage subsets in tissue repair using proteomics, bioinformatics and functional analyses. We isolated two hepatic monocyte-derived macrophage subpopulations: Ly6ChiCX3CR1lo macrophages and Ly6CloCX3CR1hi macrophages during distinct phases of acute liver injury and employed label-free proteomics approach to profile the proteome of these cells. We found that the wound healing- and endocytosis-related proteins were specifically enriched in Ly6CloCX3CR1hi macrophages. Intriguingly, 12/15-lipoxygenase (Alox15), the most strongly up-regulated protein in Ly6CloCX3CR1hi macrophages, was identified as a specific marker for these macrophages. In co-culture systems, Ly6CloCX3CR1hi macrophages specifically induced hepatocyte proliferation. Furthermore, selective depletion of this population in CD11b-diphtheria toxin receptor mice significantly delayed liver repair. Overall, our studies shed light on the functional specialization of distinct macrophage subsets in the resolution of inflammation.

2019-10-08 | PXD011958 | Pride

Multifaceted functions of SiglecF expressing neutrohpils in the exacerbation of air pollutant-induced airway inflammation

Project description:Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and implicated in asthma pathogenesis and exacerbation. However, the mechanistic link between DEP exposure and worsening asthma symptoms remains unclear. Here, we characterized a unique subset of neutrophils that express a high level of Sialic acid-binding, Ig-like lectin (Siglec)-F. DEP exposure instructs SiglecF expression on neutrophils by increasing P2X1 receptors sensing damage-associated molecular patterns (DAMPs) molecules, ATP. SiglecFhigh neutrophils stimulated by DEP release neutrophil extracellular traps (NETs) to cause tissue damage and IL-17A production, and potentiated type 2 cytokine production by producing cysteinyl leukotrienes. As a result, SiglecFhigh neutrophils worsen airway hyperresponsiveness (AHR) as well as airway inflammations. We also confirmed that siglec8, corresponding to murine SiglecF, expression increased in neutrophils from patients with asthma, and they correlated with the severity of the disease. Together, these translational findings suggest a novel SiglecF expressing neutrophils in the development of severe asthma by linking type 2 and type 3 responses.

2022-09-01 | GSE158040 | GEO

Cytokine Polarized Bone Marrow Neutrophils Drive Axon Regeneration

Project description:The adult central nervous system (CNS) has a limited capacity for self-repair. Severed CNS axons typically do not regrow. There is an unmet need for treatments specifically designed to enhance neuronal viability, facilitate CNS axon regeneration, and ultimately restore lost neurological functions to individuals with traumatic CNS injury, multiple sclerosis, and stroke, among other disorders. Here we demonstrate that both mouse and human bone marrow (BM) neutrophils upregulate markers of alternative activation, and acquire the ability to promote neurite outgrowth, following polarization with a combination of recombinant interleukin-4 (IL-4) and granulocyte-colony stimulating factor (G-CSF). Moreover, adoptively transferring IL-4/G-CSF polarized BM neutrophils into experimental models of CNS injury resulted in significant axon regeneration within the optic nerve and spinal cord. The findings reported in this paper hold significant implications for the future development of autologous myeloid cell-based therapies that may bring us closer to effective solutions for reversing CNS damage.

2023-12-01 | GSE244934 | GEO

Neutrophil immune profile guides spinal cord regeneration in zebrafish

Project description:Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-a expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.

2024-07-03 | GSE271113 | GEO

Single Cell Atlas of Injured Sciatic Nerve Tissue

Project description:Sciatic nerve crush (SNC) triggers sterile inflammation within the distal nerve and de-afferented dorsal root ganglia (DRGs). In the nerve, neutrophils and pro-inflammatory Ly6Chigh monocytes appear first and rapidly give way to Ly6Clow resolving macrophages. Transcriptional profiling of injured nerve tissue identifies six macrophage subpopulations, repair Schwann cells and mesenchymal cells as the main cell types. Macrophages at the nerve crush site are distinct from macrophages associated with degenerating nerve fibers. Monocytes and macrophages in the injured nerve “eat” apoptotic cell corpses of leukocytes and thereby contribute to an anti-inflammatory milieu. Studies with chimeric mice show that following SNC few blood-derived immune cells enter DRGs. Myeloid cells in the injured nerve, but not DRGs, express the receptor for the chemokine GM-CSF. In the absence of GM-CSF, conditioning-lesion induced regeneration of DRG neuron central projections is abrogated. Thus, a carefully orchestrated immune response in the nerve is required for conditioning-lesion induced neurorepair.

2021-03-17 | GSE153762 | GEO

Aspergillus fumigatus-derived gliotoxin impairs innate immune cell activation through modulating lipid mediator production in macrophages

Project description:Gliotoxin (GT), a major secondary metabolite and virulence factor of Aspergillus fumigatus, suppresses innate immunity and supports the evasion of host immune responses. Recently, we revealed that GT blocks leukotriene (LT)B4 formation by directly inhibiting LTA4 hydrolase (LTA4H) in activated human neutrophils and monocytes. Here, we elucidated the impact of GT on LTB4 biosynthesis and the complex lipid mediator network in human M1- and M2-like monocyte-derived macrophage (MDM) subtypes and studied the respective consequences for innate immune cell functions. Notably, in resting MDMs, GT elicited prostaglandin and 12/15-lipoxygenase product formation, although less efficient than bacterial exotoxins. In activated MDM, LTB4 formation was effectively suppressed by GT, connected to impaired macrophage phagocytic activity, and detrimental consequences for neutrophil movement and migration. Conclusively, GT impairs functions of activated innate immune cells through suppression of LTB4 formation, while GT may prime the immune system by provoking prostaglandin formation and 12/15-lipoxygenase-derived LM.

2024-11-13 | PXD045819 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data