Evidence map›Paper›PMID 34893805›Full record

ArticleJournal of Crohn's & colitis2022

Selective Targeting of Tumour Necrosis Factor Receptor 1 Induces Stable Protection from Crohn's-Like Ileitis in TNFΔARE Mice.

Rajrupa Chakraborty, Mia R Maltz, Diana Del Castillo, Purvi N Tandel, Nathalie Messih, Martha Anguiano, David D Lo

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

Article in Journal of Crohn's & colitis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 37% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

7 authors at 2 institutions in 1 country.

Rajrupa ChakrabortyDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Mia R MaltzDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Diana Del CastilloDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Purvi N TandelDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Nathalie MessihDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
Martha AnguianoDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
David D LoDivision of Biomedical Sciences, School of Medicine, University of California, Riverside School of Medicine, Riverside, CA, USA.
University of California, Riverside · USBreathe California of Sacramento Emigrant Trails · US

Funding

The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI AMITABH CHAK · 2015 to 2026
$15.6M
Genes regulating M cell differentiationR01AI063426 · NIAID · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI LO, DAVID D · 2005 to 2016
$3.6M
NIAID NIH HHS R01 AI063426NIDDK NIH HHS P30 DK097948
6 · The paper itself

Abstract

BACKGROUND AND

aimsCrohn's disease is a debilitating chronic inflammatory disorder of the mammalian gastrointestinal tract. Current interventions using anti-tumour necrosis factor [anti-TNF] biologics show long-term benefit in only half of patients. This study focused on the role of the TNF receptor 1 [TNFR1] in pathogenesis in a TNF-driven model of ileitis.

methodsWe studied TNFΔAU-rich element [ARE]/+ [TNFdARE] mice, which develop progressive ileitis similar to Crohn's ileitis. Histopathological analysis and gene expression profiling were used to characterize disease progression from 5 to 16 weeks. Mice with TNFR1 hemizygosity [TNFdARE/R1het] allowed us to assess gene dosage effects. Transcriptional profiling established inflection points in disease progression; inflammatory gene expression increased at 8 weeks with a plateau by 10 weeks, so these were selected as endpoints of treatment using the TNF biologic infliximab and the TNFR1-specific XPro1595. Differences in recruitment of cells in the lamina propria were assessed using flow cytometry.

resultsTNFdARE/R1het mice displayed stable long-term protection from disease, associated with decreased recruitment of CD11bhiF4/80lo monocytes and CD11bhiLy6Ghi neutrophils, suggesting an important role of TNFR1 signalling in pathogenesis, and indicating potential benefit from TNFR1-specific intervention. Treatment with infliximab and XPro1595 both showed a similar impact on disease in TNFdARE mice. Importantly, these beneficial effects were greatly surpassed by hemizygosity at the TNFR1 locus.

conclusionsTreatment with either infliximab or XPro1595 produced moderate protection from ileitis in TNFdARE mice. However, hemizygosity at the TNFR1 locus in TNFdARE mice showed far better protection, implicating TNFR1 signalling as a key mediator of TNF-driven disease.

Indexed as

Crohn DiseaseIleitisAnimalsDisease ProgressionInfliximabMammalsMiceReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alphaTumor Necrosis Factor InhibitorsInfliximabReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alphaTumor Necrosis Factor InhibitorsinfliximabTNFdARETNFR1XPro1595

Identifiers

PMID34893805
PMCPMC9282884
OpenAlexW4200447000

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.