Portal de Periódicos da CAPES

Fibroblastic reticular cell lineage convergence in Peyer’s patches governs intestinal immunity

2021; Nature Portfolio; Volume: 22; Issue: 4 Linguagem: Inglês

10.1038/s41590-021-00894-5

1529-2916

Alejandro Prados, Lucas Onder, Hung‐Wei Cheng, Urs Mörbe, Mechthild Lütge, Cristina Gil‐Cruz, Christian Perez‐Shibayama, Vasiliki Koliaraki, Burkhard Ludewig, George Kollias,

Immune cells in cancer

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. Kollias and colleagues examine the development of fibroblastic reticular cells (FRCs) during lymphoid organogenesis in gut Peyer's patches (PPs). They show that PP FRCs develop from two separate mesenchymal cell lineages, which converge and form mosaic microenvironments that support immune cell activation and maintain intestinal homeostasis.