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.
from sddb import Catalog
cohort = Catalog().collection("geo-gse251693")
cohort.members # the 2 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse251693")
coll.ordered_artifacts.to_dataframe() # the 2 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse251693 --dest data/Licenses: 2 NCBI GEO policy
@article{Montorsi_2024,
title = {Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue},
volume = {15},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-024-48267-4},
DOI = {10.1038/s41467-024-48267-4},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
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},
year = {2024},
month = May
}