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Splenic CD169+Tim4+ Marginal Zone Metallophilic Macrophages Are Essential for Wound Healing and Resolution of Inflammation After Myocardial Infarction

ABSTRACT: Splenic CD169+Tim4+ Marginal Zone Metallophilic Macrophages Are Essential for Wound Healing and Resolution of Inflammation After Myocardial Infarction

PROVIDER: PRJNA867567 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR20983201_1.fastq.gz	Fastqsanger.gz
	SRR20983201_2.fastq.gz	Fastqsanger.gz
	SRR20983202_1.fastq.gz	Fastqsanger.gz
	SRR20983202_2.fastq.gz	Fastqsanger.gz

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Splenic CD169+Tim4+ Marginal Zone Metallophilic Macrophages Are Essential for Wound Healing and Resolution of Inflammation After Myocardial Infarction

Project description:Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6Chi blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. Here, we establish in mice an essential role for splenic CD169+Tim4+ marginal metallophilic macrophages (MMMs) in post-MI wound healing. Splenic CD169+Tim4+ MMMs circulate in blood as Ly6Clow cells expressing express core macrophage markers and help populate CD169+Tim4+LYVE1low macrophages in the naïve heart. After acute MI, splenic MMMs augment phagocytosis and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169+Tim4+LyVE1low macrophages with an immunomodulatory and pro-resolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Pharmacological expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and cardiac remodeling. Finally, humans with acute ST-elevation MI also exhibit expansion of circulating CD169+Tim4+ macrophages. We conclude that splenic CD169+Tim4+ MMMs are required for pro-resolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.

2025-06-18 | GSE210798 | GEO

Splenic CD169+Tim4+ Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction

Project description:Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6Chi blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. Here, using a variety of in vivo murine models and orthogonal approaches, including surgical myocardial infarction, splenectomy, parabiosis, cell adoptive transfer, lineage tracing and cell tracking, RNA sequencing, and functional characterization, we establish in mice an essential role for splenic CD169+Tim4+ marginal metallophilic macrophages (MMMs) in post-MI wound healing. Splenic CD169+Tim4+ MMMs circulate in blood as Ly6Clow monocytes expressing macrophage markers and help populate CD169+Tim4+CCR2-LYVE1low macrophages in the naïve heart. After acute MI, splenic MMMs augment phagocytosis, CCR3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169+Tim4+LyVE1low macrophages with an immunomodulatory and pro-resolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-a agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Finally, humans with acute ST-elevation MI also exhibit expansion of circulating CD169+Tim4+ cells, primarily within the intermediate (CD14+CD16+) monocyte population. We conclude that splenic CD169+Tim4+ MMMs are required for pro-resolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.

2025-06-18 | GSE289921 | GEO

Splenic CD169+Tim4+ Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction

Project description:Splenic CD169+Tim4+ Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction

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Tissue proteomics of splenic marginal zone lymphoma

Project description:Splenic marginal zone lymphoma (SMZL) is a rare chronic B lymphoproliferative disease, whose molecular pathogenesis is still not well established. For the first time a proteomic approach was undertaken to analyse the protein profiles of SMZL tissue. Western blot, immunohistochemical analysis and functional data mining were also performed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that SMZL is characterized by modulation of proteins related to energetic metabolism and apoptosis pathways. We also reported specific proteins (such as biliverdin reductase A, manganese superoxide dismutase, beta-2 microglobulin, growth factor receptor-bound protein 2, acidic leucine-rich nuclear phosphoprotein 32 family member A, and SET nuclear oncogene) directly involved in NF-kBand BCR pathways, as well as in chromatin remodelling and cytoskeleton. Our findings shed new light on SMZL pathogenesis and provide a basis for the future development of novel biomarkers.

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Gene expression profiles from human splenic Marginal Zone and Naive (Follicular) B cells

Project description:Splenic Marginal Zone B cells mount innate-like T cell-independent (TI) antibody responses to blood-borne antigens upon receiving activation signals from TACI-engaging factors BAFF and APRIL. The transcriptome analysis of splenic Marginal Zone (MZ) B cells was performed to verify which transcriptional programs are enhanced in the innate-like MZ B cell subset and to study the involvement of mTOR in MZ B cells activated via TACI.

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Genomic profiling of splenic marginal zone lymphoma (SMZL)

Project description:Array-based comparative genomic hybridization comparing splenic marginal zone lymphoma (SMZL) specimens with control DNA A custom high-definition oligonucleotide microarray (4x44K, Agilent) was designed for aCGH from the online application tool eArray (version 5.3) and HD-CGH probe library (sequence source UCSC hg18 / NCBI Build 36). This custom microarray combines the capability to scan human genome-wide with an average resolution of approximately 100 Kb and to focus on regions of interest for highest resolution tiling (11 Kb-resolution for either chromosomes 3q and 7q). The array contains about 8,500 and 9,000 oligonucleotides spanning 97 Mb and 105 Mb of the 7q and the 3q chromosomes respectively. Twenty-seven SMZL specimens (9 males, 18 females) were analyzed using a dye-swap methodology to confirm the copy number variations. Two samples (one male, one female, namely M-CTRL and F-CTRL) collected from healthy volunteers blood from national Etablissement FranM-CM-'ais du Sang were used as DNA reference for aCGH experiments.

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