Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1074234 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27903866_1.fastq.gz | Fastqsanger.gz | |||
| SRR27903866_2.fastq.gz | Fastqsanger.gz | |||
| SRR27903867_1.fastq.gz | Fastqsanger.gz | |||
| SRR27903867_2.fastq.gz | Fastqsanger.gz | |||
| SRR27903868_1.fastq.gz | Fastqsanger.gz |
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Project description:Tumor-associated macrophages (TAMs), often adopting an immunosuppressive M2-like phenotype, correlate with unfavorable cancer outcomes. Our investigation unveiled elevated expression of the butyrophilin (BTN)2A1 in M2-like TAMs across diverse cancer types. We developed anti-BTN2A1 monoclonal antibodies (mAb) and notably, one clone demonstrated a robust inhibitory effect on M2-like macrophage differentiation, inducing a shift towards an M1-like phenotype both in vitro and ex vivo in TAMs from patients with cancer. Macrophages treated with this anti-BTN2A1 mAb exhibited enhanced support for T-cell proliferation and IFNγ secretion. Indeed, M1-like and M2-like macrophage differentiation involves complex signaling pathways leading to specific gene expression profiles. Typically, stimuli from the TME induce pathways including JAK/STATs, MAPK, PI3K/AKT, NOTCH and NF-κB influencing TAMs polarization. We investigated the signaling pathways activated in monocytes and M-CSF-induced M2-like macrophages upon BTN2A1 engagement using anti-BTN2A mAb5. After 30 min of treatment, we observed phosphorylation of MAPKs (i.e. ERK1/2, P38 and JNK) in CD14+ monocytes and in M2-like macrophages, unlike isotype control-treated cells. In contrast, the PI3K/AKT, JAK/STAT, and NF-kB pathways were not consistently activated after 30 min of anti-BTN2A mAb5 treatment. Since BTN2A1 lacks intrinsic kinase activity, we explored whether BTN2A1 could form complexes with molecular partners in M2-like macrophages that provide kinase activity. We prepared lysates from M2-like macrophages treated with mAb5 or with its isotype control for 30 min and performed immunoprecipitation (IP) using another anti-BTN2A mAb followed by western blotting with anti-phosphoTyrosine (pTyr). A 70 kDa was co-immunoprecipitated with BTN2A1 and revealed by the anti-pTyr in lysates from anti-BTN2A mAb5-treated M2-like macrophages. To identify which Tyrosine kinase is enriched in anti-BTN2A mAb5-treated M2-like macrophages, we performed LC-MS/MS on anti-pTyr immunoprecipitates from treated cells. Several tyrosine kinases, including P38α/δ and JNK, were enriched. Notably, SYK was also identified and matched the 72kDa molecular weight of the pTyr band co-immunoprecipitated with BTN2A1.
2024-09-02 | PXD055262 | Pride
Project description:Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function. We used microarray to support proteomic data between M1 and M2 macrophages. M1 macrophages are obtained using cell sorting of CD45+MHCII+CD8a-F4/80+ population from C57BL/6J bone marrow cell derived heterogenous cells under GM-CSF conditioning for 7 days. M2 macrophages are differentiated with 20% L929 cell supernatant for 7 days and sorted from CD45+F4/80+CD11b+ population.
2014-11-14 | E-GEOD-63245 | biostudies-arrayexpress
Project description:Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function. We used microarray to support proteomic data between M1 and M2 macrophages.
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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
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Project description:Macrophages are effector cells of the innate immune system and undergo phenotypical changes in response to organ injury and repair. They are most often classified as proinflammatory M1 and anti-inflammatory M2 macrophages. Protein arginine deiminase (PAD) enzymes, that catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification, are expressed in macrophages. However, the substrate scope of the PADs and their role in the immune cells remain not well defined. This study aims to investigate the role of PADs in the THP-1 macrophage polarization to M1 and M2 phenotype and identify the citrullinated proteins, and the modified Arg that are associated with this biological switch using mass spectrometry. Our study showed that PAD2, and to a lesser extent PAD1 and PAD4 were dominantly expressed in M1 macrophages. We showed that inhibiting PADs by BB-Cl-amidine decreased the macrophage’s polarization to M1 and increased to M2 phenotype. The process was mediated by the downregulation of proteins involved in NF-kβ pathway. Silencing of PAD2 confirmed activation to M2 macrophages through upregulation of the antiviral innate immune response and interferon signaling. 192 novel citrullination sites that belong to inflammation, cell death and DNA/RNA processing pathways were identified in M1 and M2 macrophages.
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Project description:Our previous study reported that IGFBP7 plays a role in maintaining mRNA stability of oncogenic lncRNA UBE2CP3 by RNA-RNA interaction. Clinical cohort studies had implied an oncogenic role of IGFBP7 in GC. However, the molecular mechanism of IGFBP7 in driving gastric cancer (GC) progression remains unknown. In this study, clinical analysis based on two independent cohort showed that IGFBP7 was positively associated with poor prognosis and macrophage infiltration in GC. Loss-of-function studies confirmed the oncogenic properties of IGFBP7 in regulating GC cell proliferation and invasion. Mechanismly, IGFBP7 was induced by epithelial-to-mesenchymal transition (EMT) signaling, since its expression was increased by TGF-beta treatment and reduced by overexpression of OVOL2 in GC. RNA sequencing, qRT-PCR, ELISA assay showed that IGFBP7 positively regulating FGF2 expression and secretion. Transcriptome analysis revealed that FGFR1 was downregulated in M1 macrophages but upregulated in M2 macrophages. Exogenous recombinant IGFBP7 protein in macrophages and GC cells further identified that IGFBP7 promotes macrophage polarization towards to a M2/TAM phenotype via FGF2/FGFR1/PI3K/AKT axis. Our finding highlights that IGFBP7 promotes GC by enhancing TAM infiltration through FGF2/FGFR1/PI3K/AKT axis.
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Project description:Classically (M1) and alternatively activated (M2) macrophages play distinct roles in various physiological and disease processes. Understanding the gene transcription programs that contribute to macrophage polarization along the M1/M2 spectrum may lead to new tools to detect and therapeutically manipulate macrophage phenotype. Here, we define the M1 and M2 macrophage signature through mRNA microarray. The M1 macrophage signature was defined by 629 up-regulated and 732 down-regulated genes while the M2 macrophage signature was formed by 388 up-regulated and 425 down-regulated genes. While a subset of probes was common to both M1 and M2 cells, others were exclusive to each macrophage subset. The common M1/M2 pathways were characterized by changes in various transcriptional regulators and signaling partners, including increases in Kruppel-like Factor (Klf) 4, but decreases in Klf2. To identify M1 and M2 biomarkers that help discriminate these populations, we selected genes that were increased during M1 or M2 differentiation but decreased in the opposite population. Among top novel M1-distinct genes, we identified CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2). Among top M2 genes, we found early growth response protein 2 (Egr2) and Myc. We validated these genes by Real-Time PCR and developed a CD38/Egr2-based flow cytometry assay that discriminates between M1 and M2 macrophages. Overall, this work defines the M1 and M2 signature and identifies several novel M1 and M2 genes that may be used to distinguish and manipulate M1 and M2 macrophages. Total RNA was prepared from bone marrow-derived macrophages of wild-type mice (n=2-3 independent mice) treated in M0, M1 or M2 conditions (n=2-3 replicates per condition originating from different mice)
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