Ontology highlight
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PROVIDER: PRJNA131203 | ENA |
REPOSITORIES: ENA
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Project description:Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses. This SuperSeries is composed of the SubSeries listed below.
2010-08-22 | GSE23306 | GEO
Project description:Jmjd3 is trimethyl H3K27 specific demethylase required for M2 macrophage polarization. Genomic fragments obtained from wild-type and Jmjd3-/- mouse macrophages were immunoprecipitated with anti H3K27me3 Ab, and deep sequencing was performed. wild-type and Jmjd3-/- macrophages
2010-08-22 | E-GEOD-23297 | biostudies-arrayexpress
Project description:Jmjd3 is trimethyl H3K27 specific demethylase required for M2 macrophage polarization. Genomic fragments obtained from wild-type and Jmjd3-/- mouse macrophages were immunoprecipitated with anti H3K27me3 Ab, and deep sequencing was performed.
2010-08-22 | GSE23297 | GEO
Project description:BRD4 inhibition suppressed M2 macrophage polarization. Particularly, we deeply investigated the underlying molecular mechanism of how BRD4 epigenetically regulate M2 genes expression. And finished the cut&tag experiment using BRD4, H3K27ac, IRF4 as antibody to find out the binding sites change in M2 macrophage treated with ARV825.
2024-01-09 | GSE248961 | GEO
Project description:Macrophage recruitment into tumors is correlated with poor outcomes in cancer, which correlate with STAT6-dependent M2 macrophage polarization and wound healing-type responses. Using penetrant, genetic models of neuroblastoma, we found macrophage recruitment was protective against tumor formation while disabling STAT6-mediated M2 polarization had no effect on tumorigenesis, progression or expression of key immunosuppressive pathways. Thus while macrophages are drivers of cancer in this model, non-classical M2 STAT6-independent pathways are plausible targets for cancer therapy.
2018-05-01 | GSE98763 | GEO
Project description:MYC activates different metabolic programs in a cell-type and cell-status dependent manner. However, the role of MYC in inflammatory macrophages has not yet been determined. Metabolic and molecular analyses reveal that MYC, but not HIF1, is involved in enhancing early glycolytic flux during inflammatory macrophage polarization. Ablation of MYC decreases lactate production by regulating lactate dehydrogenase (LDH) activity and causes increased inflammatory cytokines by regulating interferon regulatory factor 4 (IRF4) in response to lipopolysaccharide (LPS). Moreover, myeloid-specific deletion of MYC and pharmacological inhibition of MYC/LDH axis enhance inflammation and the bacterial clearance in vivo. These results elucidate the potential role of the MYC/LDH/IRF4 axis in inflammatory macrophages by connecting early glycolysis and inflammatory responses and suggest that modulating early glycolytic flux mediated by the MYC/LDH axis can be utilized to open new avenues for the therapeutic modulation of macrophage polarization to fight against bacterial infection.
2021-07-14 | GSE164475 | GEO
Project description:Exercise benefits M2 macrophage polarization, energy homeostasis and protects against obesity partially through exercise-induced circulating factors. Here, by unbiased quantitative proteomics on serum samples from sedentary and exercised mice, we identify parvalbumin as a circulating factor suppressed by exercise. Parvalbumin functions as a non-competitive CSF1R antagonist to inhibit M2 macrophage activation and energy expenditure in adipose tissue. More importantly, serum concentrations of parvalbumin positively correlate with obesity in mouse and human, while treating mice with a recombinant parvalbumin blocker prevents its interaction with CSF1R and promotes M2 macrophage polarization and ameliorates diet-induced obesity. Thus, although further studies are required to assess the significance of parvalbumin in mediating the effects of exercise, our results implicate parvalbumin as a potential therapeutic strategy against obesity.
2022-05-10 | PXD033582 | Pride
Project description:Macrophages form a primary immune cells population in tumor tissues and malignant ascites microenvironment (MAM). They can be activated and polarized into tumor-associated macrophages (TAM) by the embedded environment and promote tumor progression and metastasis However, the molecular mechanisms of MAM in macrophage polarization and the effects on epithelial ovarian cancer (EOC) metastatic progression remain elusive. Here, we found that that MAM modulates RhoA-GTPase-F-actin-Hippo signaling cascade in facilitating M2-like macrophage polarization that, in turn, promotes tumor dissemination. PUFA enriched magligant ascites microenvironment promote macrophage lipid oxidative phosphorylation and supression RhoA-GTPase-Yap1 axis. Genetic ablation Yap1 in macrophage exhibited M2-like polarization and enhanced ovrian tumor dissemination. Pharmacology inhibit Mst1/2 could rescue M2-like TAM polarization in MAM and alter the lipid oxidation of macrophages in MAM, more importantly, inhibit ovarian metastatic properties. Through comparasion primary TAM (P-TAM) and metastasis TAM (M-TAM), we proved that Hippo-Yap1 siganl results M-TAM with high M2/M1 ratio. These findings implicate critical functions of PUFA modulate RhoA-Hippo axis in facility TAM polarization and also suggest manipulation of PUFA metabolism or RhoA-Hippo siganl as a therapeutic strategy aganist EOC metastasis.
2024-05-01 | GSE175552 | GEO
Project description:The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNγ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4Rα protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling. Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals
2016-06-29 | E-GEOD-72000 | biostudies-arrayexpress
Project description:GM-CSF paradoxically possesses ability to differentiate both classically activated macrophages (MØs) with dominant proinflammatory function (M1-like MØs) and alternative activated MØs with strong immunosuppressive function (M2-like MØs). The intrinsic regulatory mechanism responsible for functional polarization of MØs under GM-CSF signalling remains elusive. Here we revealed that cytokine-inducible SH2-containing protein (CIS), induced by GM-CSF, is a key determinant in controlling MØ polarization. Compared to WT MØs, Cish-/- MØs gained characteristics of alternative activated MØs (M2 MØs), showing high expression of prototypic M2 markers Arginase 1, Tgm2 and YM-1; strong suppression of T cell proliferation; and low production of IL-12 and other proinflammatory cytokines¬¬. Differing from canonical IL-4/STAT6/IRF4 signaling axis of M2 induction, development of M2 MØ characteristics in Cish-/- MØs was associated with intensified STAT5 activation and consequent IRF8 downregulation. Attenuation of GM-CSF signalling via JAK inhibition and IRF8 rescue corrected certain functional defects in Cish-/- MØs. As CIS inhibition in NK and T cells promotes anti-tumour immunity, we showed that CIS deficiency enhanced the development of intra-tumoural M2 MØs and reduced CTL induction within tumour microenvironment with elevated GM-CSF. Overall, we conclude that CIS acts as an intrinsic rheostat to control intense GM-CSF signalling in order to maintain proinflammatory functions of MØs. Targeting CIS as a checkpoint in cancer immunotherapy should consider its role in regulating myeloid cell function.
2023-01-21 | PXD018390 | Pride