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Gene expression data from Peyer's patch mononuclear phagocyte system

ABSTRACT: Peyer’s patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution, ontogeny, lifespan, function and transcriptional profile of PP MPS. We show that monocytes give rise to macrophages and to lysozyme-expressing DC (LysoDC) which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures and, upon TLR7 stimulation, secrete IL-6 and TNF but no IL-10. However, unlike macrophages, LysoDC display a rapid renewal rate, strongly express genes of the MHCII presentation pathway and prime naïve helper T cells for IFNg production. Our results show that in PP, at steady state, monocytes generate both LysoDC and macrophages which display distinct features from their adjacent villus counterparts.

ORGANISM(S): Mus musculus

PROVIDER: GSE65514 | GEO | 2015/02/03

SECONDARY ACCESSION(S): PRJNA274259

REPOSITORIES: GEO

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Project description:Tissue macrophages (MPs) develop distinctive functions due to unique transcriptional programs driven by local environmental ques. In the intestine, it is known that MPs are heterogeneous cells that differentiate from blood monocytes and embryonic precursors, and are essential for homeostasis with the vast microbiome through their ability to kill invading microbes, clear apoptotic cells, and produce regulatory cytokines. However, the full extent of MP heterogeneity, their developmental relationships, and how the intestinal microbiota affects MP generation is not known. Here, we performed single cell RNA sequencing of colonic myeloid cells from specific pathogen free (SPF) and germ free (GF) C57BL/6 mice and found extensive heterogeneity of colon MP, with at least six different identifiable populations, with less heterogeneity of dendritic cells (DCs). Unsupervised modeling of developmental pathways combined with inference of gene regulatory networks suggested two major trajectories from common CCR2+ precursors resulting in CD11c+CD9+MMRintCD121b+ and CD11c-CD9intMMRhiCD121b- MP populations with unique transcription factors activities to coordinate downstream target molecules. The generation of both mature populations of colon MPs was impaired in germ-free mice, which coincided with the appearance of a dominant unique population of MPs, whereas the generation of DC populations in GF mice were unaffected or increased. Furthermore, the two major MP populations were clearly distinct from other populations regarding their gene expression profile, localization within the lamina propria, and ability to phagocytose macromolecules from the blood. These data uncover the diversity of intestinal myeloid cell populations, highlight the importance of microbiota on the unique developmental as well as anatomical and functional fates of colon MPs. We anticipate that these findings will form the basis for future studies on how tissue myeloid cell development is influenced either directly or indirectly by signals from endogenous microbiota in the intestine, as well as other tissues.

Dataset Information

Gene expression data from Peyer's patch mononuclear phagocyte system

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