Evidence map›Paper›PMID 32191633›Full record

ArticleThe Journal of clinical investigation2020

B cell-intrinsic TLR9 expression is protective in murine lupus.

Jeremy S Tilstra, Shinu John, Rachael A Gordon, Claire Leibler, Michael Kashgarian, Sheldon Bastacky, Kevin M Nickerson, Mark J Shlomchik

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.0field-weighted citation impact, top 4% of its field
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

62 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Inducible deletion ofiScience · 2024
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jeremy S TilstraDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Shinu JohnDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Rachael A GordonDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Claire LeiblerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Michael KashgarianDepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Sheldon BastackyDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Kevin M NickersonDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Mark J ShlomchikDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
University of Pittsburgh · USYale University · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
Institutional Career Development CoreKL2TR001856 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RAY, KRISTIN N, RUBIO, DORIS M · 2016 to 2025
$13.8M
Toll-Like Receptors in Systemic Autoimmune DiseaseP01AR050256 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI VIGLIANTI, GREGORY A. · 2004 to 2013
$13.4M
Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Yale Rheumatic Diseases Research Core CenterP30AR053495 · NIAMS · YALE UNIVERSITY · PI SHLOMCHIK, WARREN D · 2007 to 2017
$7.0M
THE ROLE OF B CELLS IN LUPUS NEPHRITIS AND VASCULITISR01AR044077 · NIAMS · YALE UNIVERSITY · PI SHLOMCHIK, MARK J · 1997 to 2016
$6.2M
Investigating How TLR7 Activates and TLR9 Regulates Systemic AutoimmunityR37AI118841 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2016 to 2025
$4.2M
Evaluating T cell Exhaustion in Systemic Lupus ErythematosusK08AR075056 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TILSTRA, JEREMY SCOTT · 2019 to 2023
$840k
NCATS NIH HHS KL2 TR001856NCI NIH HHS P30 CA047904NIAID NIH HHS R37 AI118841NIAMS NIH HHS K08 AR075056NIAMS NIH HHS P01 AR050256NIAMS NIH HHS P30 AR053495NIAMS NIH HHS R01 AR044077NIDDK NIH HHS P30 DK079307
6 · The paper itself

Abstract

Toll-like receptor 9 (TLR9) is a regulator of disease pathogenesis in systemic lupus erythematosus (SLE). Why TLR9 represses disease while TLR7 and MyD88 have the opposite effect remains undefined. To begin to address this question, we created 2 alleles to manipulate TLR9 expression, allowing for either selective deletion or overexpression. We used these to test cell type-specific effects of Tlr9 expression on the regulation of SLE pathogenesis. Notably, Tlr9 deficiency in B cells was sufficient to exacerbate nephritis while extinguishing anti-nucleosome antibodies, whereas Tlr9 deficiency in dendritic cells (DCs), plasmacytoid DCs, and neutrophils had no discernable effect on disease. Thus, B cell-specific Tlr9 deficiency unlinked disease from autoantibody production. Critically, B cell-specific Tlr9 overexpression resulted in ameliorated nephritis, opposite of the effect of deleting Tlr9. Our findings highlight the nonredundant role of B cell-expressed TLR9 in regulating lupus and suggest therapeutic potential in modulating and perhaps even enhancing TLR9 signals in B cells.

Indexed as

Antibody FormationAnimalsAutoantibodiesB-LymphocytesDendritic CellsDisease Models, AnimalGene Expression RegulationLupus Erythematosus, SystemicMiceMice, KnockoutSignal TransductionToll-Like Receptor 9AutoantibodiesTlr9 protein, mouseToll-Like Receptor 9AutoimmunityB cells

Identifiers

PMID32191633
PMCPMC7260024
OpenAlexW3011676113

What OpenQuestion holds

Textmetadata
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.