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Transcriptional and functional profiling defines human small intestinal macrophage subsets

ABSTRACT: Macrophages (Mf) are instrumental in maintaining immune homeostasis in the intestine, yet studies on origin and heterogeneity of human intestinal Mf are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMo), were largely replaced within 3 weeks, whereas two subsets with features of mature Mf, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptomic analysis showed that all Mf subpopulations subsets were markedly distinct from PBMo and dendritic cells (DC). Compared to PBMo, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli, but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMo.

PROVIDER: EGAS00001002093 | EGA |

REPOSITORIES: EGA

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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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2014-05-06 | E-GEOD-49877 | biostudies-arrayexpress

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Resident memory CD8 T cells persist for years in human small intestine

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2015-01-15 | E-GEOD-56525 | biostudies-arrayexpress

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.

2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress

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2022-02-02 | MSV000088772 | GNPS

GNPS_toxoplasma_mouse_11(organs,contents)_positive

Project description:Metabolites (aqueous & organic) were extracted from mouse tissues and tissues' contents (SI duodenum, SI jejunum, SI ileum, cecum, large intestine, small intestine, contents, cecum contents, large intestine contents, heart, liver, and quad) and were run by LC-MS, C8 in positive mode.

2024-08-14 | MSV000095605 | GNPS

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