Ontology highlight
ABSTRACT:
PROVIDER: PRJEB40745 | ENA |
REPOSITORIES: ENA
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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
Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of blocking GSK3 on the gene expression profile in GM-CSF-primed human monocyte derived macrophages. GSK3 inhibition skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
2025-04-16 | GSE256208 | GEO
Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of siRNA mediated knocking-down GSK3A, GSK3B or both (GSK3A/B) on the gene expression profile of GM-CSF-primed human monocyte derived macrophages. GSK3A/B knowdown skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
2025-04-16 | GSE266236 | GEO
Project description:Unstimulated (M0), M1-polarized (GM-CSF, LPS, IFNγ-stimulated), and M2-polarized (M-CSF, IL-4-stimulated) canine blood-derived macrophages were generated in vitro and investigated for differences in their transcriptome to create a basis for future investigations upon the role of macrophage polarization in dogs, a species, which has emerging importance for translational research.
2017-08-10 | E-MTAB-5458 | biostudies-arrayexpress
Project description:Granulocyte-Macrophage colony stimulating factor (GM-CSF) devlops heterogenous myeloid cell populations from bone marrow progenitor cells. In vitro generated bone marrow derived cells are excellent sources for obtaining dendritic cells or macrophages, but it is still not clear about the exact mixed population characteristics of GM-CSF grown cells. We revealed here that GM-CSF grown bone marrow cell derived attaching cells were composed of dendritic cells (GM-BMDC) as well as macrophages (GM-BMM). We compared the transcriptome profiles of these cell populations as well as M-CSF grown bone marrow derived macrophages (M-BMM). We used microarrays to detail the global profile of gene expressions between three populations of CSF-grown bone marrow derived cells: GM-CSF derived dendritic cells (GM-BMDC), GM-CSF derived macrophages (GM-BMM) and M-CSF derived macrophages (M-BMM).
2015-01-30 | GSE65425 | GEO
Project description:Granulocyte-Macrophage colony stimulating factor (GM-CSF) devlops heterogenous myeloid cell populations from bone marrow progenitor cells. In vitro generated bone marrow derived cells are excellent sources for obtaining dendritic cells or macrophages, but it is still not clear about the exact mixed population characteristics of GM-CSF grown cells. We revealed here that GM-CSF grown bone marrow cell derived attaching cells were composed of dendritic cells (GM-BMDC) as well as macrophages (GM-BMM). We compared the transcriptome profiles of these cell populations as well as M-CSF grown bone marrow derived macrophages (M-BMM). We used microarrays to detail the global profile of gene expressions between three populations of CSF-grown bone marrow derived cells: GM-CSF derived dendritic cells (GM-BMDC), GM-CSF derived macrophages (GM-BMM) and M-CSF derived macrophages (M-BMM). Bone marrow cells were differentiated for 7 days with 25 ng/ml GM-CSF or 20% L cell conditioned media as a M-CSF supplier. GM-BMDCs were sorted from MHCIIhighF4/80low population and GM-BMMs were sorted in the MHCIIlowF4/80high population. M-BMMs were sorted from CD11b+F4/80+ population.
2015-01-30 | E-GEOD-65425 | biostudies-arrayexpress
Project description:Caspases, which are key effectors of apoptosis, have demonstrated non-apoptotic functions. One of these functions is the differentiation into macrophages of peripheral blood monocytes exposed to Colony-Stimulating Factor-1 (CSF1). Conversely, GM-CSF induces the differentiation of monocytes into macrophages in a caspase-independent manner. Macrophages generated by CSF1 and GM-CSF have distinct polarity. Macrophage polarization plays an important role in the pathogenesis of diverse human diseases as cancer, leading us to explore if caspase inhibition would affect macrophage polarization. To explore the role of caspases in CSF1 differentiation, we used human monocytes sorted from buffy coats treated by cytokines. We reported that caspase inhibition delays the ex vivo differentiation of peripheral blood monocytes exposed to CSF1 and modifies the phenotype of generated macrophages, e.g. cell shape, surface markers. Moreover, by RNAseq, we observed that the macrophages generated in presence of CSF1 and QVD are different from CSF1-treated monocytes and from GM-CSF-treated monocytes. Cell cycle and focal adhesion-related pathway genes were selectively down-regulated. This study confirms the importance of caspase activation in CSF1 differentiation.
2024-01-01 | E-MTAB-5752 | biostudies-arrayexpress
Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.
2020-02-19 | PXD012794 | Pride
Project description:Despite the importance of tumor-associated macrophages (TAMs) in modulating anti-tumor immunity, the molecular determinants of their functional phenotypes remain elusive. Through a large-scale CRISPR screen, we discovered that tumor-derived lactic acid, PGE2, and GM-CSF collaboratively shape the highly conserved but mutually exclusive TAM phenotypes: MHC-II+ and angiogenic TAMs. Mechanistically, the dichotomous nature of these two phenotypes is driven by the antagonistic interactions between lactic acid/PGE2 and GM-CSF. Lactic acid and PGE2 coordinately induce the angiogenic gene program while suppressing the GM-CSF-induced MHC-II program at chromatin level. This mechanism leads to distinct spatial distribution of TAMs, with angiogenic TAMs in lactate-rich hypoxic regions and MHC-II+ TAMs outside these areas. Furthermore, in vivo genetic perturbation of TAMs showed that shifting TAMs to an interferon responsive program, triggered by Adar inactivation, substantially potentiates anti-tumor immunity. Our findings suggest a conserved mechanism of TAM polarization and a potential approach for reprogramming TAMs in immunotherapy.
2025-08-03 | GSE269027 | GEO
Project description:Comparison of the transcriptome macrophages derived from CD14+ human monocyte-derived macrophages generated in the presence of M-CSF (M-Mphage) or GM-CSF (GM-Mphage) and MTX.
2023-06-14 | GSE228475 | GEO