Evidence map›Paper›PMID 40998762›Full record

ArticleNature communications2025

A specific gene expression program underlies antigen archiving by lymphatic endothelial cells in mammalian lymph nodes.

Ryan M Sheridan, Thu A Doan, Cormac J Lucas, Tadg S Forward, Ira Fleming, Valerie M Olsen, Abrianna M Qvale, Bennett J Davenport, Kristen Zarrella, Michael G Harbell and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Ryan M SheridanDepartment of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.
Thu A DoanDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-4838-0343
Cormac J LucasDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-6904-8219
Tadg S ForwardDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0001-5920-1702
Ira FlemingDepartment of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-4691-6933
Valerie M OlsenDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0009-0005-0601-8222
Abrianna M QvaleDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.
Bennett J DavenportDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0001-8155-191X
Kristen ZarrellaDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-3142-6664
Michael G HarbellDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
Aspen Uecker-MartinDepartment of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.
Thomas E MorrisonDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-1811-2938
Jay R HesselberthDepartment of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-6299-179X
Beth A Jirón TamburiniDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA. Beth.tamburini@cuanschutz.edu.ORCID http://orcid.org/0000-0003-1991-231X

Funding

Nanopore analysis of transfer RNA forms and functionsR35GM119550 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Jay R Hesselberth · 2016 to 2026
$4.5M
Cooperation between lymphatic stroma and hematopoietic cells shapes protective immunityR01AI121209 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Beth Ann Tamburini · 2016 to 2026
$4.5M
Biochemistry at single-cell resolution: a new approach to understand functional heterogeneityR01AG071467 · NIA · UNIVERSITY OF COLORADO DENVER · PI HESSELBERTH, JAY R · 2020 to 2024
$3.2M
Clearance of Blood-Borne ArbovirusesR01AI148144 · NIAID · UNIVERSITY OF COLORADO DENVER · PI MORRISON, THOMAS E · 2020 to 2025
$2.3M
PD-L1 reverse signaling in dermal DCs promotes DC migration and skin immunity to cutaneous pathogensR01AI155474 · NIAID · UNIVERSITY OF COLORADO DENVER · PI TAMBURINI, BETH ANN · 2020 to 2024
$2.3M
Molecular tracking of antigen following vaccinationR21AI155929 · NIAID · UNIVERSITY OF COLORADO DENVER · PI TAMBURINI, BETH ANN · 2021 to 2022
$417k
NIAID NIH HHS R01 AI121209NIAID NIH HHS R01 AI148144NIAID NIH HHS R01 AI155474NIAID NIH HHS R21 AI155929NIA NIH HHS R01 AG071467NIGMS NIH HHS R35 GM119550
6 · The paper itself

Abstract

Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens. Here, we address questions of how LECs achieve durable antigen archiving and whether LECs with high levels of antigen express unique transcriptional programs. We use single cell sequencing in dissociated LN tissue and spatial transcriptomics to quantify antigen levels in LEC subsets and dendritic cell populations at multiple time points after immunization and determine that ceiling and floor LECs archive antigen for the longest duration. We identify, using spatial transcriptomics, antigen positive LEC-dendritic cell interactions. Using a prime-boost strategy we find increased antigen levels within LECs after a second immunization demonstrating that LEC antigen acquisition and archiving capacity can be improved over multiple exposures. Using machine learning we define a unique transcriptional program within archiving LECs that predicts LEC archiving capacity in independent mouse and human data sets. We test this modeling, showing we can predict lower levels of LEC antigen archiving in chikungunya virus-infected mice and demonstrate in vivo the accuracy of our prediction. Collectively, our findings establish unique properties of LECs and a defining transcriptional program for antigen archiving that can predict antigen archiving capacity in different disease states and organisms.

Indexed as

AntigensEndothelial CellsLymph NodesAnimalsDendritic CellsFemaleGene Expression ProfilingHumansMiceMice, Inbred C57BLSingle-Cell AnalysisTranscriptomeAntigens

Identifiers

PMID40998762
PMCPMC12462432

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.