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

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 used single-cell RNA sequencing (scRNA-seq) to characterize human intestinal NMPs and identify cell type-specific GPCRs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240900 | GEO | 2024/10/08

REPOSITORIES: GEO

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

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

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

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

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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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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).

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CX3CR1<sup>+</sup> mononuclear phagocytes control immunity to intestinal fungi.

Project description:Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn's disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

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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.

2019-10-04 | GSE138364 | GEO

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2012-10-01 | E-GEOD-35565 | biostudies-arrayexpress

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