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CITE-seq Analysis of Dendritic Cells in the Gut-Draining Lymph Node in anti-IL10R-treated mice with LIPSTIC Labeling of Akkermansia muciniphila Presenting Cells

ABSTRACT: Commensal-specific T cells contribute to tissue homeostasis within the intestines, and can influence disease pathology in the context of both cancer and autoimmunity. Antigen presenting cells play a critical role in influencing the differentiation of these T cells, but how the complex network of antigen presenting cells in the intestines drives commensal-specific T cells towards a variety of differentiation trajectories remains poorly understood. We examined the priming of T cells specific for the intestinal commensal bacterial species Akkermansia muciniphila, using the LIPSTIC system combined with single-cell RNA-sequencing to identify the APCs that prime A. muciniphila-specific T cells both at homeostasis when it elicits T follicular helper cells, and during inflammation, when it also elicits TH17 and TH1 cells. We found that A. muciniphila-specific T cells were primed by several transcriptionally distinct subpopulations of migratory cDC2s in both contexts. The identity of these subpopulations did not change with inflammation, but the distribution of presentation across the subpopulations shifted, with increased presentation by inflammatory cDC2s favoring TH1 and TH17 polarization. These results reveal how distinct T cell differentiation trajectories can be determined through varied interactions with multiple, functionally distinct subpopulations of APCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE313299 | GEO | 2026/01/05

REPOSITORIES: GEO

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Project description:Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota. Keywords: Analysis of target gene regulation by using microarrays Adult germ-free female NMRI-KI mice (45 – 65 days) were used for bacterial mono-association. Two bacterial strains were used in this study, A. muciniphila MucT (ATTC BAA-835) and L. plantarum WCFS1 (NCIMB 8826). A. muciniphila was grown anaerobically in a basal mucin based medium and L. plantarum was grown anaerobically at 37°C in Man-Rogosa-Sharpe broth (MRS; Le Pont de Claix, France). After 7 days of colonization, mice were killed by cervical dislocation and terminal ileum, cecum and ascending colon specimens were sampled.

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CITE-seq Analysis of Dendritic Cells in the Gut-Draining Lymph Node in anti-IL10R-treated mice with LIPSTIC Labeling of Akkermansia muciniphila Presenting Cells

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