Evidence map›Paper›PMID 34804036›Full record

ArticleFrontiers in immunology2021

Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes.

Pamela J Lincez, Iryna Shanina, Marc S Horwitz

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. How loss-of-function mutations inJournal of translational autoimmunity · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. 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

3 authors at 2 institutions in 1 country.

Pamela J LincezMichael Smith Laboratories, The University of British Columbia, Vancouver, BC, Canada.
Iryna ShaninaDepartment of Microbiology & Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC, Canada.
Marc S HorwitzDepartment of Microbiology & Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC, Canada.
University of British Columbia · CACanada's Michael Smith Genome Sciences Centre · CA

Funding

CIHR
6 · The paper itself

Abstract

Seemingly redundant in function, melanoma differentiation-associated protein 5 (MDA5) and toll-like receptor- 3 (TLR3) both sense RNA viruses and induce type I interferon (IFN-I). Herein, we demonstrate that changes in sensing of the same virus by MDA5 and TLR3 can lead to distinct signatures of IFN-α and IFN-ß resulting in different disease outcomes. Specifically, infection with a diabetogenic islet β cell-tropic strain of coxsackievirus (CB4) results in diabetes protection under reduced MDA5 signaling conditions while reduced TLR3 function retains diabetes susceptibility. Regulating the induction of IFN-I at the site of virus infection creates a local site of interferonopathy leading to loss of T cell regulation and induction of autoimmune diabetes. We have not demonstrated another way to prevent T1D in the NOD mouse, rather we believe this work has provided compounding evidence for a specific control of IFN-I to drive a myriad of responses ranging from virus clearance to onset of autoimmune diabetes.

Indexed as

AnimalsCoxsackievirus InfectionsCytokinesDiabetes Mellitus, Type 1Enterovirus B, HumanFemaleInterferon-Induced Helicase, IFIH1MaleMiceMice, Inbred NODMice, TransgenicToll-Like Receptor 3CytokinesIfih1 protein, mouseInterferon-Induced Helicase, IFIH1TLR3 protein, mouseToll-Like Receptor 3autoimmunitycoxsackievirusdiabetesinterferoninterferonopathyMDA5TLR3

Identifiers

PMID34804036
PMCPMC8602094
OpenAlexW3211475678

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.