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Gene expression profiles of each subset of human intestinal mononuclear phagocytes (MNPs)

ABSTRACT: MNPs play an important role in intestinal homeostasis. The interaction of intestinal metabolites with G protein-coupled receptors (GPCRs) expressed on human MNPs has not been well characterized. We report here that GPR31 is specifically expressed in cDC1 in human ileal MNPs by bulk RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272657 | GEO | 2024/10/08

REPOSITORIES: GEO

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Gene expression profile of human intestinal mononuclear phagocytes (MNPs) at the single-cell level

Project description:MNPs play an important role in intestinal homeostasis. The interaction of intestinal metabolites with G protein-coupled receptors (GPCRs) expressed on human MNPs has not been well characterized. We used single-cell RNA sequencing (scRNA-seq) to characterize human intestinal NMPs and identify cell type-specific GPCRs.

2024-10-08 | GSE240900 | GEO

Gene expression profile of human intestinal mononuclear phagocytes (MNPs) at the single-cell level II

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Gene expression profiles of each subset of human intestinal mononuclear phagocytes (MNPs)

Project description:Gene expression profiles of each subset of human intestinal mononuclear phagocytes (MNPs)

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Effect of pyruvate (PA), lactate (LA), or 12-hydroxyeicosatetraenoic acid (12-HETE) stimulation on type1 conventional dendritic cells (cDC1) from the human ileum

Project description:We here report that GPR31 is specifically expressed in cDC1 in human intestinal mononuclear phagocytes. Since GPR31 has been previously reported to be activated by PA, LA, and 12-HETE, RNA-seq was performed to analyze the transcriptional changes in human ileal cDC1 under the stimulation of PA, LA, or 12-HETE.

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Transcriptional characterization of mononuclear phagocytes (MNP) in blood and BAL of healthy and sarcoidosis patients

Project description:Pulmonary sarcoidosis is an inflammatory disease characterized by granuloma formation and heterogeneous clinical outcome. TNF is a proinflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages (AMs) have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells (DCs) that despite their central role in inflammation are poorly studied in sarcoidosis. We performed in-depth phenotypic, functional and transcriptomic analysis of MNPs subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls.

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Gene expression profile of human intestinal mononuclear phagocytes (MNPs) at the single-cell level

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Mononuclear phagocytes in neonatal Peyer's patches

Project description:The small intestine contains lymph node-like structures termed Peyer’s patches (PP). In adult mice they contain active germinal centers reminiscent of active crosstalk with microbiota. In neonatal mice, however, homeostatic immune activation does not take place. We wanted to test whether immune maturation in neonatal mice is stalled due to a reduced presence or function of antigen presenting mononuclear phagocytes (MNP). Thus we subjected PP MNP of postnatal day (PND) 11 and adult mice to scRNAseq in steady state or after immune activation with the TLR7 agonist R848 that induces type I interferon and TNFa after oral gavage. Our results show an altered subset distribution of MNP in neonatal mice (predominance of cDC1 and cDC2b, reduced proportion of cDC2a) and a reduced potential to take up microorganisms and process/present antigen as well as decreased type I interferon mediated gene expresseion. R848 administration could partly overcome this maturation defect of neonatal MNP by increasing the proportion of CCR7+ mature cDC as well as upregulation of interferon I dependent genes.

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Transcriptomic analysis and high dimensional phenotypic mapping of mononuclear phagocytes in mesenteric lymph nodes reveal differences between ulcerative colitis and Crohn’s disease

Project description:Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRPα+ MNPs in CD and UC MLNs. Methods: Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRPα+ MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients. Results: Elevated frequencies of CD14+CD64+CD163+ [Mono/MΦ-like] MNPs displaying monocyte/ MΦ morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14-CD64-CD163- [DC-like] cells was augmented relative to Mono/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ- like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123+ plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163+ clusters were revealed in Mono/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD. Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.

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Gene expression profile of human intestinal mononuclear phagocytes (MNPs) at the single-cell level II

Project description:Gene expression profile of human intestinal mononuclear phagocytes (MNPs) at the single-cell level II

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Human intestinal DC and MNP

Project description:Parallel subpopulations of CD11c+ MNPs present in the mouse intestine similarly exist in the human intestine (Fig. 6A and Ref. (Merad et al., 2013)). To evaluate whether these distinct subpopulations of MNPs from human intestinal tissue functioned similarly, we examined the phenotypic properties of CD103+ DCs and CD14+ MNPs (which express CX3CR1 (Kamada et al., 2008)) within the CD11c+ MHCII+ fraction of LPMCs (Fig. 6B). In contrast to CD103+ DCs, CD14+ MNPs expressed CD64 as well as higher levels of CD86. Consistent with the phenotypic characterization of these subsets, transcriptional analysis of these populations by RNA-seq revealed higher levels of CLEC9A, XCR1, and CD207 expression in the CD103+ cells, while MERTK, STAB1, and CX3CR1 were higher in the CD14+ cells (Fig. 6C). We tested the potential of these subsets to induce IL-22 production by co-culturing TLR-stimulated CD14+ MNPs and CD103+ DCs from human intestinal resections with intestinal ILCs. Intracellular cytokine staining at 18 hours revealed that the CD14+ MNP were more effective than the CD103+ DCs at stimulating IL-22 production by ILCs (Fig. 6D). Neither cell population induced significant IL-17 or IFNg production by ILCs (Fig. 6D, 6E).

2014-07-15 | GSE59386 | GEO

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