Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA362954 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MФ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
2017-01-24 | GSE93970 | GEO
Project description:Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes—pro-inflammatory and pro-resolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas pro-resolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemo-immunotherapy, mesenchymal-like tumors expanded pro-resolution macrophages through phagocytosis/efferocytosis, ω-3 fatty-acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T-cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory macrophages and neutrophils that produced prostaglandins via ω-6 fatty-acid pathways. Knocking down ELOVL5—an elongase involved in ω-3 and ω-6 metabolism—mitigated both neutrophil- and macrophage-mediated immunosuppression. These distinct axes, driven by dysregulated inflammation and resolution programs, converged to undermine therapy-induced immunosurveillance; however, targeting their shared upstream regulators may overcome these resistance mechanisms.
2026-02-05 | GSE294252 | GEO
Project description:Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.
2010-07-07 | E-GEOD-22373 | biostudies-arrayexpress
Project description:Tumor microenvironment (TME) is an active player in malignant growth and spread. Changes in the composition and structure of TME and extracellular matrix can result in either suppression or facilitation of malignant tumor growth. Carcinoma‐associated fibroblasts, bone marrow-derived multipotent mesenchymal stromal cells (BMMSCs), tumor associated macrophages and other inflammatory cells all affect the composition of TME, proliferation and survival of cancer cells, angiogenesis, invasion and metastasis. The objective of this work was to investigate the effect of the interaction between bone marrow-derived BMMSCs and human oral tongue squamous cell carcinoma (OTSCC) cells in the processes of invasion and gene expression. Co-cultures of OTSCC cancer cells and BMMSCs in 3D organotypic invasion assay were used in addition to cell culture, immunological, microarray, and RNA interference techniques. Total number of 4 samples were analyzed. 2 replicates of cultured human oral tongue squamous cell carcinoma (OTSCC) cells, and 2 replicates of OTSCC cells co-cultured with bone marrow-derived multipotent mesenchymal stromal cells
2013-12-01 | E-GEOD-44458 | biostudies-arrayexpress
Project description:<p> Skeletal healing requires the coordinated resolution of inflammation and precise lineage commitment of mesenchymal progenitors, yet the mechanisms coupling these processes remain incompletely defined. Here, we reveal that lymphatic vessels in bone serve as dynamic orchestrators bridging inflammatory clearance with stromal fate determination during regeneration. Using lineage tracing in Lyve1-creERT2; tdTomato mice and genetic ablation approaches, we demonstrate that injury-induced lymphangiogenesis is essential for timely osteogenesis. Prior depletion of lymphatic endothelial cells (LECs) exacerbates inflammation and impairs bone regeneration following injury. Notably, we identify Lyve1highmacrophages as lymphatic endothelial-like cells capable of transdifferentiation following efferocytosis. Mechanistically, engulfment of apoptotic cells activates fatty acid β-oxidation, increasing acetyl-CoA level that drive histone acetylation at the Lyve1 and Vegfc promoters, thereby licensing the macrophages-to-LECs transition. During the remodeling phase, lymphatic vessels help maintain local lipid homeostasis. Lymphatic impairment during bone repair leads to accumulation of polyunsaturated fatty acid-containing phosphatidylethanolamines (PE-PUFAs), which stabilize PPARγ through ZDHHC4-mediated palmitoylation. This process blocks ubiquitin-proteasome degradation and skews LepR+ bone mesenchymal stromal cells (BMSCs) toward adipogenesis at the expense of osteogenesis. Age-related lymphatic insufficiency recapitulates this pathological cascade, manifesting as impaired drainage, systemic lipid dysregulation, and compromised bone quality. Collectively, our findings establish lymphatic vessels, reconstructed by macrophages-to-LECs transdifferentiation, as stage-specific niche that guides osteogenic-adipogenic fate decision of BMSCs through lymphatic drainage capacity in skeletal repair.</p>
2026-01-17 | MTBLS13645 | MetaboLights
Project description:We isolated non-hematopoietic cells from fibrotic and non-fibrotic human bone marrow and perfomed scRNAseq on them. We identified 3 different stromal populations and 2 populations of hematopoietic progenitors. Our analysis revealed mesenchymal stromal cells (MSC) as pro-fibrotic cells. MSCs were functionally reprogrammed with loss of their progenitor status and acquisition of a pro-fibrotic phenotype in the fibrotic bone marrow. Additionally, stromal cells exhibited an upregulation of pro-inflammatory mediators like S100A8/A9.
2020-11-03 | GSE156640 | GEO
Project description:Macrophages are essential for tissue homeostasis, orchestrating the initiation and resolution of both innate and adaptive immunity with profound impacts on protective immunity and immune-mediated pathological damage. Macrophages are heterogeneous subsets. During the inflammatory response, they include both pro-inflammatory subsets and subsets that promote inflammation resolution, and different macrophage subsets play distinct roles in the dynamic processes at different time points. In the current study, we found that a subset of TGM2+ macrophages with inflammation-resolving properties gradually increases during the inflammation resolution phase in the LPS-induced endotoxin shock model. The peak expression of the TGM2 gene occurs mainly during the inflammation resolution phase. Additionally, transcriptome analysis revealed that compared with wild-type (WT) macrophages, TGM2-deficient macrophages exhibited a significant upregulation of pro-inflammatory signatures and a marked downregulation of lipid metabolic synthesis processes. In lipid rescue experiments, we found that the elevated inflammation phenotype of TGM2-deficient macrophages could be restored. Moreover, a significant anti-inflammatory function of this macrophage subset was observed in mouse models of severe disease, enterocolitis, and endotoxin shock. We uncover an inflammatory remodeling of the neuro-metabolic landscape in macrophages, whereby serotonin induces TGM2-mediated serotonylation of in AKT1.
2025-12-15 | GSE313189 | GEO
Project description:Periodontitis is a chronic inflammatory condition marked by an imbalance between proinflammatory and proresolution mediators, which affects the tissues supporting the teeth. Maresin1 (MaR1) is a specialized pro-resolving lipid mediator (SPM) produced by macrophages, known for its role in regulating inflammatory processes. This study aimed to investigate the effects of MaR1 at varying concentrations on human gingival mesenchymal stem cells (hGMSCs) within inflammatory environments.
2024-11-20 | PXD058076 |
Project description:Syndecan-3 positively regulates the pro-inflammatory function of macrophages
| PRJNA1141950 | ENA
Project description:Epoxygenases belong to the cytochrome P450 family and they generate epoxyeicosatrienoic acids (EETs) known to have anti-inflammatory effects but little is known about their role in macrophage function. By high-throughput sequencing of RNA (RNA-seq) in primary macrophages derived fromrodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major rat macrophage epoxygenase Cyp2j4 (orthologue of human CYP2J2),resulted inreduced EET synthesis. Cyp2j4-/-macrophages have relatively increased PPARγ levels and show a pro-fibrotic transcriptome,displayingover-expression of a specific subset of genes (260 transcripts) primarily involved in extracellular matrix, with fibronectin being the most abundantly expressed transcript.Fibronectin expression is under the control of epoxygenase activity in human and rat primary macrophages. In keeping with the invitro findings, Cyp2j4-/- rats show up-regulation of type I collagen following unilateral ureter obstruction (UUO) of the kidney and quantitative proteomics analysis (LC-MS/MS) showed increased renal type I collagen and fibronectin protein abundance resulting from experimentally induced crescentic glomerulonephritis in these rats. Taken together, these results identify the rat epoxygenase Cyp2j4 as a determinant of a pro-fibrotic macrophage transcriptome that could have implications in various inflammatory conditions depending on macrophage function. Gene expression profile generated for macrophages in wild type and Cyp2j4 KO WKY rats
2015-02-10 | E-GEOD-65715 | biostudies-arrayexpress