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

Montorsi, Lucia ; Pitcher, Michael J ; Zhao, Yuan ; Dionisi, Chiara ; Demonti, Alicia ; Tull, Thomas J ; Dhami, Pawan ; Ellis, Richard J ; Bishop, Cynthia and Sanderson, Jeremy D , et al. (2024) In Nature Communications 15(1). p.4051-4051
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Animals, Humans, Mice, B-Lymphocytes/immunology, Gastrointestinal Microbiome/immunology, Endodeoxyribonucleases/metabolism, Dendritic Cells/immunology, Lymphoid Tissue/immunology, Female, Mice, Inbred C57BL, Intestinal Mucosa/immunology, Male
in
Nature Communications
volume
15
issue
1
pages
4051 - 4051
publisher
Nature Publishing Group
external identifiers
  • scopus:85193205703
  • pmid:38744839
ISSN
2041-1723
DOI
10.1038/s41467-024-48267-4
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
014dee57-9974-4752-82b6-dee36c38f5f4
date added to LUP
2024-05-21 09:34:36
date last changed
2024-06-19 05:41:44
@article{014dee57-9974-4752-82b6-dee36c38f5f4,
  abstract     = {{<p>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.</p>}},
  author       = {{Montorsi, Lucia and Pitcher, Michael J and Zhao, Yuan and Dionisi, Chiara and Demonti, Alicia and Tull, Thomas J and Dhami, Pawan and Ellis, Richard J and Bishop, Cynthia and Sanderson, Jeremy D and Jain, Sahil and D'Cruz, David and Gibbons, Deena L and Winkler, Thomas H and Bemark, Mats and Ciccarelli, Francesca D and Spencer, Jo}},
  issn         = {{2041-1723}},
  keywords     = {{Animals; Humans; Mice; B-Lymphocytes/immunology; Gastrointestinal Microbiome/immunology; Endodeoxyribonucleases/metabolism; Dendritic Cells/immunology; Lymphoid Tissue/immunology; Female; Mice, Inbred C57BL; Intestinal Mucosa/immunology; Male}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{1}},
  pages        = {{4051--4051}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-48267-4}},
  doi          = {{10.1038/s41467-024-48267-4}},
  volume       = {{15}},
  year         = {{2024}},
}