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Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
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Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
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Journal Article
Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
2024
Overview
Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.
Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14
/ 14/19
/ 14/63
/ 38
/ 38/1
/ 38/91
/ 49/39
/ 82/1
/ Animals
/ Antigens
/ Bacteria
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ Domes
/ Endodeoxyribonucleases - genetics
/ Endodeoxyribonucleases - metabolism
/ Female
/ Gastrointestinal Microbiome - immunology
/ Gut-associated lymphoid tissues
/ Humanities and Social Sciences
/ Humans
/ Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
/ Immunology in the Medical Area (including Cell and Immunotherapy)
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - microbiology
/ Lymphoid Tissue - immunology
/ Lymphoid Tissue - metabolism
/ Male
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Science
