Τίτλος:
Fibroblastic reticular cell lineage convergence in Peyer’s patches governs intestinal immunity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Fibroblastic reticular cells (FRCs) determine the organization of lymphoid organs and control immune cell interactions. While the cellular and molecular mechanisms underlying FRC differentiation in lymph nodes and the splenic white pulp have been elaborated to some extent, in Peyer’s patches (PPs) they remain elusive. Using a combination of single-cell transcriptomics and cell fate mapping in advanced mouse models, we found that PP formation in the mouse embryo is initiated by an expansion of perivascular FRC precursors, followed by FRC differentiation from subepithelial progenitors. Single-cell transcriptomics and cell fate mapping confirmed the convergence of perivascular and subepithelial FRC lineages. Furthermore, lineage-specific loss- and gain-of-function approaches revealed that the two FRC lineages synergistically direct PP organization, maintain intestinal microbiome homeostasis and control anticoronavirus immune responses in the gut. Collectively, this study reveals a distinct mosaic patterning program that generates key stromal cell infrastructures for the control of intestinal immunity. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.
Συγγραφείς:
Prados, A.
Onder, L.
Cheng, H.-W.
Mörbe, U.
Lütge, M.
Gil-Cruz, C.
Perez-Shibayama, C.
Koliaraki, V.
Ludewig, B.
Kollias, G.
Περιοδικό:
Nature Immunology
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Λέξεις-κλειδιά:
animal cell; animal experiment; animal model; article; cell fate; cell lineage; Coronavirinae; fibroblast; homeostasis; immune response; intestine flora; male; mouse; mouse embryo; mouse model; nonhuman; Peyer patch; reticulum cell; single cell RNA seq; stroma cell; animal; C57BL mouse; cell communication; cell culture; Coronavirus infection; disease model; fibroblast; gene expression profiling; gene expression regulation; host pathogen interaction; immunology; intestine mucosa; knockout mouse; metabolism; microbiology; mucosal immunity; Murine hepatitis virus; pathogenicity; Peyer patch; phenotype; single cell analysis; small intestine; virology, transcriptome, Animals; Cell Communication; Cell Lineage; Cells, Cultured; Coronavirus Infections; Disease Models, Animal; Fibroblasts; Gastrointestinal Microbiome; Gene Expression Profiling; Gene Expression Regulation, Developmental; Host-Pathogen Interactions; Immunity, Mucosal; Intestinal Mucosa; Intestine, Small; Mice, Inbred C57BL; Mice, Knockout; Murine hepatitis virus; Peyer's Patches; Phenotype; Single-Cell Analysis; Transcriptome
DOI:
10.1038/s41590-021-00894-5
