Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue.

Autor: Montorsi L; School of Immunology and Microbial Sciences, King's College London, London, UK., Pitcher MJ; School of Immunology and Microbial Sciences, King's College London, London, UK., Zhao Y; School of Immunology and Microbial Sciences, King's College London, London, UK., Dionisi C; School of Immunology and Microbial Sciences, King's College London, London, UK., Demonti A; School of Immunology and Microbial Sciences, King's College London, London, UK.; École Normale Supérieure de Lyon, Claude Bernard Lyon 1 University, Lyon, France., Tull TJ; St. John's Institute of Dermatology, King's College London, London, UK., Dhami P; Genomics Research Platform and Single Cell Laboratory at Guy's and St Thomas' NHS Foundation Trust, London, UK., Ellis RJ; Advanced Cytometry Platform (Flow Core), Research and Development Department at Guy's and St Thomas' NHS Foundation Trust, London, UK., Bishop C; Advanced Cytometry Platform (Flow Core), Research and Development Department at Guy's and St Thomas' NHS Foundation Trust, London, UK., Sanderson JD; School of Immunology and Microbial Sciences, King's College London, London, UK.; Department of Gastroenterology, Guy's and St Thomas' Foundation Trust, London, UK., Jain S; Louise Coote Lupus Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK., D'Cruz D; School of Immunology and Microbial Sciences, King's College London, London, UK.; Louise Coote Lupus Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK., Gibbons DL; School of Immunology and Microbial Sciences, King's College London, London, UK., Winkler TH; Division of Genetics, Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Bemark M; Department of Translational Medicine - Human Immunology, Lund University, Malmö, Sweden.; Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden., Ciccarelli FD; Cancer Systems Biology Laboratory, The Francis Crick Institute, London, UK., Spencer J; School of Immunology and Microbial Sciences, King's College London, London, UK. jo.spencer@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 14; Vol. 15 (1), pp. 4051. Date of Electronic Publication: 2024 May 14.
DOI: 10.1038/s41467-024-48267-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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