ArticleJournal of immunology (Baltimore, Md. : 1950)2013
TLR3, TRIF, and caspase 8 determine double-stranded RNA-induced epithelial cell death and survival in vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- TRIF-dependent signaling and its role in liver diseases.Frontiers in cell and developmental biology · 2024Review
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis.Cell death & disease · 2022Article
- Adaptive differentiation promotes intestinal villus recovery.Developmental cell · 2022Article
- Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk.Scientific reports · 2021Article
- Cell death pathways: intricate connections and disease implications.The EMBO journal · 2021Review
- RNA Signaling in Pulmonary Arterial Hypertension-A Double-Stranded Sword.International journal of molecular sciences · 2020Review
- Nucleic Acid Sensors and Programmed Cell Death.Journal of molecular biology · 2020Review
- The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.International review of cell and molecular biology · 2020Review
- Aichi Virus Induces Antiviral Host Defense in Primary Murine Intestinal Epithelial Cells.Viruses · 2019Article
- Toll-Like Receptor 3-TRIF Pathway Activation byInfection and immunity · 2019Article
- Soluble TNF-like weak inducer of apoptosis (TWEAK) enhances poly(I:C)-induced RIPK1-mediated necroptosis.Cell death & disease · 2018Article
- The double stranded RNA analog poly-IC elicits both robust IFN-λ production and oncolytic activity in human gastrointestinal cancer cells.Oncotarget · 2018Article
- Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection.Journal of virology · 2018Article
- Inflammatory cell death in intestinal pathologies.Immunological reviews · 2017Review
- Double-stranded RNA induces chicken T-cell lymphoma apoptosis by TRIF and NF-κB.Scientific reports · 2017Article
- Studying the Effect of Downregulating Autophagy-Related Gene LC3 on TLR3 Apoptotic Pathway Mediated by dsRNA in Hepatocellular Carcinoma Cells.Cancer research and treatment · 2017Article
- TLR3 signaling is downregulated by a MAVS isoform in epithelial cells.Cellular immunology · 2016Article
- Both the anti- and pro-apoptotic functions of villin regulate cell turnover and intestinal homeostasis.Scientific reports · 2016Article
- Caspase-8 regulates the expression of pro- and anti-inflammatory cytokines in human bone marrow-derived mesenchymal stromal cells.Immunity, inflammation and disease · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
TLR3 signaling is activated by dsRNA, a virus-associated molecular pattern. Injection of dsRNA into mice induced a rapid, dramatic, and reversible remodeling of the small intestinal mucosa with significant villus shortening. Villus shortening was preceded by increased caspase 3 and 8 activation and apoptosis of intestinal epithelial cells (IECs) located in the mid to upper villus with ensuing luminal fluid accumulation and diarrhea because of an increased secretory state. Mice lacking TLR3 or the adaptor molelcule TRIF mice were completely protected from dsRNA-induced IEC apoptosis, villus shortening, and diarrhea. dsRNA-induced apoptosis was independent of TNF signaling. Notably, NF-κB signaling through IκB kinase β protected crypt IECs but did not protect villus IECs from dsRNA-induced or TNF-induced apoptosis. dsRNA did not induce early caspase 3 activation with subsequent villus shortening in mice lacking caspase 8 in IECs but instead caused villus destruction with a loss of small intestinal surface epithelium and death. Consistent with direct activation of the TLR3-TRIF-caspase 8 signaling pathway by dsRNA in IECs, dsRNA-induced signaling of apoptosis was independent of non-TLR3 dsRNA signaling pathways, IL-15, TNF, IL-1, IL-6, IFN regulatory factor 3, type I IFN receptor, adaptive immunity, as well as dendritic cells, NK cells, and other hematopoietic cells. We conclude that dsRNA activation of the TLR3-TRIF-caspase 8 signaling pathway in IECs has a significant impact on the structure and function of the small intestinal mucosa and suggest signaling through this pathway has a host protective role during infection with viral pathogens.
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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.