ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
The death receptor 3/TL1A pathway is essential for efficient development of antiviral CD4⁺ and CD8⁺ T-cell immunity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- The Therapeutic Potential of Targeting TL1A in a Spectrum of Inflammatory Disorders.Journal of inflammation research · 2026Review
- Review
- Clinical Model Based on DR3 Promoter Methylation for Predicting Short-Term Mortality in Patients with Acute-on-Chronic Hepatitis B Liver Failure.International journal of general medicine · 2025Article
- TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway.Current medical science · 2024Article
- The ever-expanding role of cytokine receptor DR3 in T cells.Cytokine · 2024Review
- Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation.Experimental & molecular medicine · 2023Review
- COL3A1: Potential prognostic predictor for head and neck cancer based on immune-microenvironment alternative splicing.Cancer medicine · 2023Article
- TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial-Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma.Frontiers in immunology · 2022Article
- Generation of highly proliferative, rejuvenated cytotoxic T cell clones through pluripotency reprogramming for adoptive immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- TNFSF15 Promotes Antimicrobial Pathways in Human Macrophages and These Are Modulated by TNFSF15 Disease-Risk Variants.Cellular and molecular gastroenterology and hepatology · 2021Article
- TL1A-DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1-Specific T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus.Nature communications · 2020Article
- Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy.Immune network · 2020Review
- TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity.Frontiers in immunology · 2019Review
- Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive Immune Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Death Receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation.Cellular immunology · 2017Article
- T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria.PLoS pathogens · 2017Article
- Article
- Death Receptor 3 Promotes Chemokine-Directed Leukocyte Recruitment in Acute Resolving Inflammation and Is Essential for Pathological Development of Mesothelial Fibrosis in Chronic Disease.The American journal of pathology · 2016Article
- Characterization of death receptor 3-dependent aortic changes during inflammatory arthritis.Pharmacology research & perspectives · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Death receptor 3 (DR3, TNFRSF25), the closest family relative to tumor necrosis factor receptor 1, promotes CD4(+) T-cell-driven inflammatory disease. We investigated the in vivo role of DR3 and its ligand TL1A in viral infection, by challenging DR3-deficient (DR3(KO)) mice and their DR3(WT) littermates with the β-herpesvirus murine cytomegalovirus or the poxvirus vaccinia virus. The phenotype and function of splenic T-cells were analyzed using flow cytometry and molecular biological techniques. We report surface expression of DR3 by naive CD8(+) T cells, with TCR activation increasing its levels 4-fold and altering the ratio of DR3 splice variants. T-cell responses were reduced up to 90% in DR3(KO) mice during acute infection. Adoptive transfer experiments indicated this was dependent on T-cell-restricted expression of DR3. DR3-dependent CD8(+) T-cell expansion was NK and CD4 independent and due to proliferation, not decreased cell death. Notably, impaired immunity in DR3(KO) hosts on a C57BL/6 background was associated with 4- to 7-fold increases in viral loads during the acute phase of infection, and in mice with suboptimal NK responses was essential for survival (37.5%). This is the first description of DR3 regulating virus-specific T-cell function in vivo and uncovers a critical role for DR3 in mediating antiviral immunity.
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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.