Evidence map›Paper›PMID 30516351›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2019

Adenosine 2a Receptor Signal Blockade of Murine Autoimmune Arthritis via Inhibition of Pathogenic Germinal Center-Follicular Helper T Cells.

Shirdi E Schmiel, Lokesh A Kalekar, Na Zhang, Thomas W Blankespoor, Londyn J Robinson, Daniel L Mueller

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.5field-weighted citation impact, top 31% 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

13 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Adenosine and Inflammation: Here, There and Everywhere.International journal of molecular sciences · 2021
    Review
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

6 authors at 1 institution in 1 country.

Shirdi E SchmielUniversity of Minnesota Medical School, Minneapolis.
Lokesh A KalekarUniversity of Minnesota Medical School, Minneapolis.
Na ZhangUniversity of Minnesota Medical School, Minneapolis.
Thomas W BlankespoorUniversity of Minnesota Medical School, Minneapolis.
Londyn J RobinsonUniversity of Minnesota Medical School, Minneapolis.ORCID 0000-0002-0961-4020
Daniel L MuellerUniversity of Minnesota Medical School, Minneapolis.
University of Minnesota Medical Center · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4M
Type I interferons in tolerance in the steady stateP01AI035296 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MUELLER, DANIEL L · 1993 to 2023
$31.1M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Lupus Link MinnesotaNCI NIH HHS P30 CA077598NIAID NIH HHS P01 AI035296NIAID NIH HHS T32 AI007313
6 · The paper itself

Abstract

objectiveCD4 germinal center (GC)-follicular helper T (Tfh) cells are important in the pathogenesis of autoimmune arthritis. Previous studies have shown that adenosine 2a receptor (A2aR; Adora2a) signaling can divert CD4 T cells away from the GC-Tfh cell lineage during the primary response to foreign antigens. This study was undertaken to examine the effects of A2aR signaling on CD4 T cells during the recognition of self antigen in a murine model of autoimmune arthritis.

methodsWild-type and Adora2a-deficient mouse KRN T cell receptor-transgenic CD4 T cells specific for glucose-6-phosphate isomerase (GPI)/I-A

resultsCGS treatment inhibited the development of arthritis and differentiation of KRN GC-Tfh cells, blocked the appearance of high-affinity GPI-specific and IgG1 isotype class-switched polyclonal plasmablasts, and led to a reduction in serum titers of anti-GPI IgG1. In addition, therapeutic administration of CGS after the onset of arthritis blocked further disease progression in association with reductions in the number of KRN GC-Tfh cells and anti-GPI IgG1 serum titers.

conclusionStrong A2aR signaling diverts autoreactive CD4 T cell differentiation away from the GC-Tfh cell lineage, thus reducing help for the differentiation of dangerous autoreactive B cells that promote arthritis. These data in a mouse model of autoimmune arthritis suggest that A2aR and its downstream signaling pathways in CD4 T cells may be promising therapeutic targets for interfering with potentially dangerous autoreactive GC-Tfh cell differentiation.

Indexed as

AdenosineAdenosine A2 Receptor AgonistsAdoptive TransferAnimalsArthritis, ExperimentalAutoantigensAutoimmune DiseasesCD4-Positive T-LymphocytesCytokinesDisease Models, AnimalGerminal CenterGlucose-6-Phosphate IsomeraseMiceMice, KnockoutMice, TransgenicPhenethylamines2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosineAdenosineAdenosine A2 Receptor AgonistsAdora2a protein, mouseAutoantigensCytokinesGlucose-6-Phosphate IsomeraseGpi1 protein, mousePhenethylaminesReceptor, Adenosine A2AReceptors, Antigen, T-Cell, alpha-beta

Identifiers

PMID30516351
PMCPMC6483839
OpenAlexW2903512872

What OpenQuestion holds

Textmetadata
LicenceTDM
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.