ArticleThe Journal of clinical investigation2011
RNA sensor-induced type I IFN prevents diabetes caused by a β cell-tropic virus in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pooled it
- Extracellular Vesicles Released by Picornavirus-Infected Cells Modify Antiviral Immune Cell Responses.Journal of extracellular vesicles · 2026Article
- Review
- Inborn errors of TLR3- or MDA5-dependent type I IFN immunity in children with enterovirus rhombencephalitis.The Journal of experimental medicine · 2021Article
- Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes.Frontiers in immunology · 2021Article
- Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology.Basic research in cardiology · 2020Review
- Genetic Susceptibility of the Host in Virus-Induced Diabetes.Microorganisms · 2020Review
- Enteroviruses and T1D: Is It the Virus, the Genes or Both which Cause T1D.Microorganisms · 2020Review
- The location of sensing determines the pancreatic β-cell response to the viral mimetic dsRNA.The Journal of biological chemistry · 2020Article
- Article
- Sources of Type I Interferons in Infectious Immunity: Plasmacytoid Dendritic Cells Not Always in the Driver's Seat.Frontiers in immunology · 2019Review
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- The Macrophage in Cardiac Homeostasis and Disease: JACC Macrophage in CVD Series (Part 4).Journal of the American College of Cardiology · 2018Review
- Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling.Frontiers in microbiology · 2018Review
- HCFC2 is needed for IRF1- and IRF2-dependentThe Journal of experimental medicine · 2017Article
- Where Does Inflammation Fit?Current cardiology reports · 2017Review
- Recurrent rhinovirus infections in a child with inherited MDA5 deficiency.The Journal of experimental medicine · 2017Article
- Macrophages and dendritic cells in islets of Langerhans in diabetic autoimmunity: a lesson on cell interactions in a mini-organ.Current opinion in immunology · 2016Review
- Nucleic acid sensing and innate immunity: signaling pathways controlling viral pathogenesis and autoimmunity.Current clinical microbiology reports · 2016Article
- Type 1 diabetes genetic susceptibility and dendritic cell function: potential targets for treatment.Journal of leukocyte biology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Viral infections have been linked to the onset of type I diabetes (T1D), with viruses postulated to induce disease directly by causing β cell injury and subsequent release of autoantigens and indirectly via the host type I interferon (IFN-I) response triggered by the virus. Consistent with this, resistance to T1D is associated with polymorphisms that impair the function of melanoma differentiation associated gene-5 (MDA5), a sensor of viral RNA that elicits IFN-I responses. In animal models, triggering of another viral sensor, TLR3, has been implicated in diabetes. Here, we found that MDA5 and TLR3 are both required to prevent diabetes in mice infected with encephalomyocarditis virus strain D (EMCV-D), which has tropism for the insulin-producing β cells of the pancreas. Infection of Tlr3-/- mice caused diabetes due to impaired IFN-I responses and virus-induced β cell damage rather than T cell-mediated autoimmunity. Mice lacking just 1 copy of Mda5 developed transient hyperglycemia when infected with EMCV-D, whereas homozygous Mda5-/- mice developed severe cardiac pathology. TLR3 and MDA5 controlled EMCV-D infection and diabetes by acting in hematopoietic and stromal cells, respectively, inducing IFN-I responses at kinetically distinct time points. We therefore conclude that optimal functioning of viral sensors and prompt IFN-I responses are required to prevent diabetes when caused by a virus that infects and damages the β cells of the pancreas.
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Identifiers
What OpenQuestion holds
Registered trials
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.