Affinage

TNFRSF25

Tumor necrosis factor receptor superfamily member 25 · UniProt Q93038

Length
417 aa
Mass
45.4 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFRSF25 (DR3) is a death-domain-containing TNF receptor superfamily member expressed predominantly on lymphocytes that functions as a context-dependent costimulatory and pro-survival receptor linking innate and adaptive immune responses. Its sole confirmed ligand, TL1A (TNFSF15), triggers recruitment of TRADD, TRAF2, and RIP into a signaling complex that activates NF-κB, PI3K/Akt, and MAPK pathways; NF-κB-dependent upregulation of c-IAP2 prevents DR3-mediated apoptosis, converting the death-domain signal into a pro-survival and proliferative output (PMID:12882979, PMID:11911831). DR3 is constitutively expressed at high levels on CD4+FoxP3+ regulatory T cells, where agonistic signaling drives rapid, selective Treg expansion through TCR- and IL-2R-dependent Akt activation in a Galectin-9-dependent manner, conferring protection in models of allergy, transplant rejection, GVHD, and colitis (PMID:20890040, PMID:27233964, PMID:28877989). Beyond T cells, TL1A–DR3 signaling on ILC3s activates p38 MAPK to induce GM-CSF and modulate intestinal inflammation, and on fibroblasts activates Rho signaling to promote intestinal fibrosis, establishing DR3 as a pleiotropic regulator of mucosal immunity and tissue remodeling (PMID:31358760, PMID:33097818).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Cloning of TNFRSF25 established it as a death-domain-containing receptor with lymphocyte-restricted expression and extensive alternative splicing, raising the question of how isoform switching regulates its function after T cell activation.

    Evidence Molecular cloning, overexpression apoptosis assay in 293T cells, RT-PCR/Northern blot isoform profiling across tissues

    PMID:9114039

    Open questions at the time
    • Functional significance of individual splice isoforms undefined
    • Endogenous ligand unknown at this point
    • Mechanism of splicing switch upon T cell activation not characterized
  2. 2002 High

    Identification of TL1A as the cognate ligand for DR3 resolved the receptor's upstream activation signal and demonstrated that TL1A–DR3 engagement activates NF-κB, induces apoptosis, and costimulates T cells for IL-2 responsiveness and cytokine secretion.

    Evidence Ligand-receptor binding assays, NF-κB reporter assays, apoptosis assays, T cell costimulation with TR6-Fc antagonist

    PMID:11911831

    Open questions at the time
    • Proximal signaling complex composition not yet defined
    • Balance between apoptosis and survival signaling unexplained
    • Physiological relevance in vivo not tested
  3. 2003 High

    Biochemical dissection of the DR3 signaling complex revealed recruitment of TRADD, TRAF2, and RIP, and showed that NF-κB-mediated c-IAP2 upregulation switches DR3 from a death signal to a survival signal, resolving how a death-domain receptor promotes proliferation rather than apoptosis.

    Evidence Co-immunoprecipitation of DR3 complex, NF-κB and MAPK inhibitors, c-IAP2 RNAi in TF-1 cells

    PMID:12882979

    Open questions at the time
    • Role of individual MAPKs (ERK, JNK, p38) in T cell costimulation not distinguished
    • Signaling in primary T cells vs cell lines not compared
    • Structural basis of complex assembly unknown
  4. 2006 High

    Functional studies demonstrated that TL1A–DR3 preferentially costimulates memory CD4+ T cells for IFN-γ production via synergy with IL-12/IL-18 and TCR signals, and confirmed that activation-dependent splicing upregulates the transmembrane DR3 isoform, linking isoform regulation to effector function.

    Evidence T cell proliferation/cytokine assays, RT-PCR isoform analysis, two murine ileitis models

    PMID:16698931

    Open questions at the time
    • Splicing regulatory machinery not identified
    • Relative contribution of individual cytokine synergy pathways unclear in vivo
  5. 2008 High

    Genetic knockout studies in mice proved that DR3 on T cells is required for TL1A-mediated immunopathology in EAE and allergic lung disease, and identified Th17 cells as a key effector subset with elevated DR3 expression, while showing DR3 is dispensable for initial T cell priming.

    Evidence DR3-knockout and TL1A-knockout mice in EAE and allergic lung inflammation models, T cell transfer, flow cytometry

    PMID:18411337 PMID:18571443

    Open questions at the time
    • Mechanism by which DR3 selectively promotes Th17 expansion not defined at signaling level
    • Role of DR3 on non-T cell populations not addressed
  6. 2010 High

    Discovery that DR3 is constitutively expressed on FoxP3+ Tregs and that agonistic DR3 antibody drives rapid, selective Treg expansion in vivo through TCR-, IL-2R-, and Akt-dependent but rapamycin-insensitive signaling fundamentally reframed DR3 as a Treg costimulatory receptor with therapeutic potential.

    Evidence Agonistic mAb 4C12 treatment in mice, signaling pathway inhibitors, allergic lung inflammation model

    PMID:20890040

    Open questions at the time
    • Molecular basis of rapamycin insensitivity not explained
    • Whether Treg expansion reflects proliferation vs survival not distinguished
    • Treg suppressive mechanism specifics undefined
  7. 2012 Medium

    DR3 agonist-mediated Treg expansion was shown to have therapeutic efficacy in cardiac allograft rejection and HSV stromal keratitis, broadening the translational relevance and demonstrating that combination with Galectin-9 enhances regulatory outcomes.

    Evidence Agonistic anti-DR3 antibody in heart transplant and HSV-1 keratitis mouse models, flow cytometry, histopathology

    PMID:22811539 PMID:22902792

    Open questions at the time
    • Mechanism of Galectin-9 synergy with DR3 not molecularly defined
    • Long-term graft tolerance not established
    • Human Treg responsiveness to DR3 agonism not tested
  8. 2016 High

    Loss-of-function studies in DR3−/− and TL1A−/− mice demonstrated that constitutive TL1A–DR3 signaling is required to maintain intestinal Tregs during mucosal damage, and its absence tips the balance toward pathogenic Th17 responses, establishing DR3 as a homeostatic regulator of mucosal immunity.

    Evidence DR3-KO and TL1A-KO mice in DSS colitis and Salmonella infection models, flow cytometry for Treg/Th17 balance

    PMID:27233964

    Open questions at the time
    • Cell-intrinsic vs extrinsic requirement for DR3 on Tregs in the gut not separated
    • Contribution of ILCs not assessed
  9. 2017 Medium

    Identification of Galectin-9 as a direct binding partner of DR3's extracellular domain, required for DR3 agonist-mediated Treg expansion and disease protection, revealed a co-receptor requirement for DR3 signaling on Tregs.

    Evidence Direct binding assay, Galectin-9-KO mice in EAE and allergic lung models, in vitro Treg stimulation

    PMID:28877989

    Open questions at the time
    • Whether Galectin-9 modifies DR3 signaling complex composition unknown
    • Structural basis of DR3–Galectin-9 interaction not resolved
    • Relevance to non-Treg DR3 signaling not tested
  10. 2019 High

    DR3 signaling on ILC3s was shown to activate p38 MAPK leading to GM-CSF production that drives IL-23-dependent ILC3 depletion and colitis exacerbation, revealing a cell-type-specific pro-inflammatory DR3 signaling axis distinct from its Treg-expanding role.

    Evidence Agonistic anti-DR3 antibody, GM-CSF/IL-23 blockade, ILC3-depleted mice, DSS and anti-CD40 colitis models

    PMID:31358760

    Open questions at the time
    • Molecular basis for differential pathway selection (p38 in ILC3 vs Akt in Tregs) not defined
    • Role of TRADD/TRAF2 complex in ILC3 not assessed
  11. 2020 High

    Cell-type-specific knockout demonstrated that TL1A–DR3 signaling directly on fibroblasts, independent of immune cells, promotes intestinal fibrosis through Rho pathway activation, extending DR3 function beyond the immune system to tissue remodeling.

    Evidence Fibroblast-specific DR3 conditional KO (Rag−/−Dr3ΔCol1a2), RNA-seq of TL1A-stimulated fibroblasts, Rho inhibition

    PMID:33097818

    Open questions at the time
    • Specific Rho GTPase family member(s) involved not identified
    • Whether fibroblast DR3 uses TRADD/TRAF2 complex not tested
    • Relevance to human fibrotic disease not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of DR3 signaling complex assembly, the molecular determinants that select between pro-survival (NF-κB/Akt) and pro-inflammatory (p38/Rho) outputs in different cell types, and whether DR3 agonism can be therapeutically harnessed for selective Treg expansion in humans.
  • No crystal structure of DR3 ectodomain or DR3–TL1A complex
  • Mechanism of cell-type-specific pathway selection (Akt vs p38 vs Rho) unknown
  • Human clinical validation of DR3 agonist-driven Treg expansion absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 2
Partners
LGALS9RIPK1TNFSF15TRADDTRAF2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TL1A (TNFSF15) is the cognate ligand for DR3 (TNFRSF25) and decoy receptor TR6/DcR3. TL1A binding to DR3 induces NF-κB activation and apoptosis in DR3-expressing cell lines, and acts as a T cell costimulator increasing IL-2 responsiveness and secretion of proinflammatory cytokines. TR6-Fc protein antagonizes these signaling events. Ligand-receptor binding assays, NF-κB reporter assays, apoptosis assays, cytokine secretion assays in vitro and in vivo T cell costimulation experiments Immunity High 11911831
2003 TL1A-DR3 interaction triggers formation of a signaling complex containing TRADD, TRAF2, and RIP, and activates NF-κB and ERK/JNK/p38 MAPK pathways. NF-κB activation prevents DR3-mediated apoptosis via upregulation of c-IAP2; inhibition of c-IAP2 by RNAi sensitizes cells to TL1A-induced apoptosis. Co-immunoprecipitation of DR3 signaling complex, NF-κB pathway inhibitors, MAPK inhibitors, RNAi knockdown of c-IAP2, apoptosis assays in TF-1 cells The Journal of biological chemistry High 12882979
1997 TNFRSF25 (LARD) contains a death domain and induces spontaneous apoptosis when overexpressed in 293T cells. Expression is lymphocyte-specific (T and B cells). Alternative pre-mRNA splicing generates at least 11 isoforms; full-length membrane-bound isoform predominates after T cell activation in a programmed splicing switch. Molecular cloning, overexpression in 293T cells (apoptosis assay), RT-PCR/Northern blot for isoform characterization, expression analysis across cell types Proceedings of the National Academy of Sciences of the United States of America High 9114039
2008 DR3 (TNFRSF25) is the receptor responsible for TL1A-induced T cell costimulation. DR3 is required on T cells for immunopathology, local T cell accumulation, and cytokine production in EAE and allergic lung inflammation models. DR3 is not required for in vivo T cell priming or effector subset polarization. Dendritic cells are identified as the likely source of TL1A during T cell activation. DR3-deficient mouse (genetic knockout), EAE and allergic lung inflammation disease models, T cell transfer experiments, flow cytometry Immunity High 18571443
2008 DR3 (TNFRSF25) expression is selectively elevated in Th17 cells. TL1A promotes proliferation of effector Th17 cells via DR3. TL1A-deficient dendritic cells have reduced capacity to support Th17 differentiation and proliferation. TL1A is required for optimal Th17 differentiation and effector function during EAE. TL1A-knockout mouse generation, EAE model, flow cytometry for Th17 markers, DC-T cell co-culture assays The Journal of experimental medicine High 18411337
2010 TNFRSF25 (TNFR25) is constitutively and highly expressed by CD4+FoxP3+ Tregs. Agonistic signaling through TNFR25 (via antibody 4C12) induces rapid and selective expansion of pre-existing Tregs in vivo (up to 30-35% of CD4+ T cells within 4 days). This Treg expansion requires TCR engagement with MHC class II, IL-2 receptor signaling, and Akt signaling, but not CD80/CD86 costimulation, and is rapamycin-insensitive. TNFR25-expanded Tregs suppress allergic lung inflammation in vivo. Agonistic monoclonal antibody (4C12) treatment in mice, flow cytometry for Treg expansion, signaling inhibitor studies, allergic lung inflammation mouse model The Journal of clinical investigation High 20890040
2006 TL1A and DR3 interaction promotes IFN-γ secretion in activated T cells. TL1A acts preferentially on memory CD4+/CD45RBlo T cells to induce proliferation. TL1A synergizes with IL-12/IL-18 pathway and with low-dose TCR stimulation to induce IFN-γ via an IL-18-independent pathway. DR3 mRNA undergoes alternative splicing upon lymphocyte activation, upregulating the complete/transmembrane form. RT-PCR for DR3 isoform analysis, T cell proliferation assays, cytokine secretion assays (IFN-γ), pathway inhibitor studies, two murine ileitis models Proceedings of the National Academy of Sciences of the United States of America High 16698931
2000 TWEAK does not interact with WSL-1/TRAMP (DR3) in in vitro binding assays. TWEAK binds to cells not expressing DR3 on their surface and retains biological activity in cells from DR3 knockout mice, demonstrating that DR3 is not the major receptor for TWEAK. In vitro binding assays with human and murine TWEAK, cell surface expression analysis, DR3 knockout mouse cells FEBS letters High 11094155
2011 TNFRSF25 triggering by TL1A promotes proliferation and accumulation of antigen-specific CD8+ T cells and their differentiation into CTLs in vivo. TNFRSF25 also functions as a costimulatory receptor for memory CD8+ T cells, enhancing secondary expansion of endogenous antigen-specific memory CD8+ T cells. Ectopic TL1A expression on plasmacytomas, OT-I TCR transgenic T cell adoptive transfer, in vivo TL1A treatment, flow cytometry for CTL differentiation and proliferation European journal of immunology Medium 21688261
2014 Atsttrin (a progranulin-derived molecule) directly binds to TNFRSF25 (DR3). The first three cysteine-rich domains (CRD) in the extracellular portion of DR3 are required for Atsttrin binding. Atsttrin inhibits the interaction between DR3 and TL1A, suppresses TL1A-stimulated target gene expression, and neutralizes TL1A-enhanced osteoclastogenesis in vitro. Direct binding assays (ELISA/pulldown), domain deletion mutants of DR3, competitive binding assay, osteoclastogenesis assay, DSS colitis model PloS one Medium 24651300
2012 TNFRSF25 agonist antibody (4C12)-mediated Treg expansion in vivo delays cardiac allograft rejection, associated with increased Foxp3+ Tregs within the graft and decreased infiltration of inflammatory cells. In vivo TNFRSF25 agonist antibody treatment, fully MHC-mismatched heterotopic heart transplant model, flow cytometry, histopathology, qRT-PCR Transplantation Medium 22902792
2013 TNFRSF25 ligation by TL1A leads to recruitment of TRAF2 and TRADD in primary T cells, with downstream activation of NFκB and PI3K/Akt signaling pathways. These pathways are dependent on coordinated engagement of the TCR and IL-2 receptor, leading to constitutive proliferation of CD4+FoxP3+ Tregs. Co-immunoprecipitation, signaling pathway inhibitors, primary T cell stimulation assays Immunologic research Medium 24242819
2017 The extracellular region of DR3 directly binds to Galectin-9, and Galectin-9 associates with DR3 in Tregs. DR3 agonist-mediated expansion of CD4+Foxp3+ Tregs and suppression of EAE and allergic lung inflammation requires Galectin-9, as protective effects are lost in Galectin-9-/- mice. Direct binding assay (Galectin-9 binding to extracellular DR3), in vitro stimulation of Galectin-9-/- Tregs, EAE and allergic lung inflammation models in Galectin-9-/- mice, flow cytometry Journal of immunology Medium 28877989
2019 Activation of DR3 signaling by an agonistic anti-DR3 antibody increases GM-CSF production from ILC3s through the p38 MAPK pathway. GM-CSF causes accumulation of eosinophils, neutrophils and myeloid cells, leading to loss of ILC3s from the intestine in an IL-23-dependent manner and exacerbating colitis. Neutralization of TL1A by soluble DR3 ameliorates DSS and anti-CD40 antibody-induced colitis. Agonistic anti-DR3 antibody treatment, GM-CSF and IL-23 blockade/overexpression experiments, ILC3-depleted mice, DSS and anti-CD40 colitis models, flow cytometry Nature communications High 31358760
2020 Direct TL1A signaling through DR3 on fibroblasts promotes intestinal fibrosis in vivo, independent of immune cell DR3 signaling. TL1A activates the Rho signal transduction pathway in fibroblasts, and inhibition of this pathway modulates TL1A-mediated fibroblast activation and migration. T cell transfer colitis model in Rag-/-, Rag-/-Dr3-/-, and fibroblast-specific DR3 knockout (Rag-/-Dr3ΔCol1a2) mice, RNA-sequencing of TL1A-stimulated fibroblasts, Rho pathway inhibition, collagen deposition assays Scientific reports High 33097818
2006 The DR3 gene promoter CpG island is specifically hypermethylated in rheumatoid arthritis synovial cells, inhibiting DR3 gene expression and DR-3 protein levels, which may provide resistance to apoptosis in RA synovial cells. Bisulfite genomic sequencing, methylation-specific PCR, luciferase reporter assays with forced methylation by bacterial methylase Sss I, Western blotting Arthritis and rheumatism Medium 16508942
2005 TL1A and DR3 signaling in macrophage/foam cells induces pro-atherogenic cytokines (TNF-α, MCP-1, IL-8) and matrix metalloproteinase-9 (MMP-9) when combined with IFN-γ stimulation, suggesting a role for the TL1A-DR3 pathway in atherogenesis. Anti-DR3 monoclonal antibody stimulation and recombinant TL1A treatment of THP-1 macrophage-like cells, cytokine/chemokine ELISA, MMP-9 measurement, immunohistochemistry of carotid plaques Cytokine Low 15760679
2016 DR3 signaling protects against acute DSS colitis; DR3-/- mice show more severe mucosal inflammation and increased mortality. DR3-/- mice are compromised in maintaining CD4+CD25+Foxp3+ regulatory T cells in response to acute mucosal damage, leading to upregulation of Th17 effector responses. TL1A-/- mice similarly show increased susceptibility and reduced Treg numbers. DR3-/- and TL1A-/- mice, DSS colitis model, Salmonella typhimurium infection model, flow cytometry for Treg and Th17 populations Journal of immunology High 27233964
2019 DR3 activation by TL1A-Ig fusion protein or agonistic antibody (4C12) leads to Treg expansion with upregulation of activation markers ICOS, KLRG-1, PD-1, CD103, and Ki-67. DR3 agonist-mediated Treg expansion in donor mice significantly improves GVHD outcomes in MHC-mismatched hematopoietic cell transplantation recipients. TL1A-Ig fusion protein and agonistic antibody treatment, bioluminescent imaging, flow cytometry, RNA-sequencing, GVHD mouse model Frontiers in immunology Medium 31379829
2022 TL1A-DR3 axis contributes to airway remodeling in asthma. Non-secreted TL1A (nsTL1A) expressed by airway epithelial cells facilitates TGF-β-induced remodeling. Knockdown of DR3 or TL1A decreases fibrosis-associated protein expression. DR3 knockdown or TL1A knockout partly reverses airway remodeling in OVA-asthma mouse model. Downstream signaling is mediated via the NF-κB pathway. DR3 siRNA, TL1A siRNA, truncated plasmid overexpression in BEAS-2B cells, DR3 knockdown and TL1A knockout mouse asthma model, RNA-sequencing Allergy, asthma & immunology research Medium 35255540
2012 Pre-treatment with TNFRSF25 agonistic antibody (MAbT25) before HSV infection effectively reduces severity of subsequent stromal keratitis lesions by expanding Foxp3+ Tregs. Combination of MAbT25 with galectin-9 provides superior lesion control by expanding regulatory T cells expressing CD103 while markedly reducing IFN-γ-producing effector CD4+ T cells. Agonistic TNFRSF25 antibody treatment in HSV-1 corneal infection model, flow cytometry, galectin-9 combination treatment Journal of virology Medium 22811539

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity 523 11911831
2006 Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer research 251 16452231
1999 Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate cancer and prostatic diseases 199 12496841
2010 Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PloS one 190 20062804
2008 TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease. The Journal of experimental medicine 187 18411337
2008 The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases. Immunity 179 18571443
1997 LARD: a new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing. Proceedings of the National Academy of Sciences of the United States of America 175 9114039
2011 Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA. The EMBO journal 158 22179700
2013 Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation. Biochemical pharmacology 157 23416117
2008 TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway. Nature structural & molecular biology 155 18776903
2013 Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Carcinogenesis 149 24067903
2006 Role of TL1A and its receptor DR3 in two models of chronic murine ileitis. Proceedings of the National Academy of Sciences of the United States of America 137 16698931
2010 Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation. The Journal of clinical investigation 132 20890040
1989 T cells sensitized to synthetic HLA-DR3 peptide give evidence of continuous presentation of denatured HLA-DR3 molecules by HLA-DP. The Journal of experimental medicine 132 2784477
2014 High-lard and high-fish-oil diets differ in their effects on function and dynamic behaviour of rat hepatic mitochondria. PloS one 113 24663492
2003 TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells. The Journal of biological chemistry 105 12882979
2012 Systemic buffers inhibit carcinogenesis in TRAMP mice. The Journal of urology 101 22704445
2002 Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Biochemical and biophysical research communications 97 12470639
2006 Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells. Arthritis and rheumatism 96 16508942
2019 TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity. Frontiers in immunology 92 30972074
2011 The RNA helicase Mtr4p modulates polyadenylation in the TRAMP complex. Cell 86 21663793
2009 TRAMP complex enhances RNA degradation by the nuclear exosome component Rrp6. The Journal of biological chemistry 85 19955569
2009 Resistance to celiac disease in humanized HLA-DR3-DQ2-transgenic mice expressing specific anti-gliadin CD4+ T cells. Journal of immunology (Baltimore, Md. : 1950) 83 19494267
2013 Nuclear RNA surveillance: role of TRAMP in controlling exosome specificity. Wiley interdisciplinary reviews. RNA 79 23417976
2006 The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. Carcinogenesis 78 17052998
2005 Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. Cytokine 71 15760679
2016 Identification of pork flavour precursors from enzyme-treated lard using Maillard model system assessed by GC-MS and partial least squares regression. Meat science 69 27792915
2004 Genistein alters growth factor signaling in transgenic prostate model (TRAMP). Molecular and cellular endocrinology 67 15149738
1983 HLA-DR3 and DR7 in coeliac disease: immunogenetic and clinical aspects. Gut 64 6603391
2014 The molecular architecture of the TRAMP complex reveals the organization and interplay of its two catalytic activities. Molecular cell 62 25175027
2012 RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex. Proceedings of the National Academy of Sciences of the United States of America 61 22532666
2013 The role of TL1A and DR3 in autoimmune and inflammatory diseases. Mediators of inflammation 59 24453414
2014 Progranulin-derived Atsttrin directly binds to TNFRSF25 (DR3) and inhibits TNF-like ligand 1A (TL1A) activity. PloS one 58 24651300
1985 HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants. The Journal of experimental medicine 58 2413154
2011 Triggering of TNFRSF25 promotes CD8⁺ T-cell responses and anti-tumor immunity. European journal of immunology 56 21688261
2010 Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proceedings of the National Academy of Sciences of the United States of America 54 20696927
2019 Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Nature communications 53 31358760
2010 Defective NKT cell activation by CD1d+ TRAMP prostate tumor cells is corrected by interleukin-12 with α-galactosylceramide. PloS one 52 20593019
2009 The role of SPARC in the TRAMP model of prostate carcinogenesis and progression. Oncogene 52 19597474
2009 The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome. PloS one 52 19707589
2008 Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM. Journal of immunology (Baltimore, Md. : 1950) 52 18832702
2019 Influence of lard-based diacylglycerol on rheological and physicochemical properties of thermally induced gels of porcine myofibrillar protein at different NaCl concentrations. Food research international (Ottawa, Ont.) 51 31882115
2017 Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9. Journal of immunology (Baltimore, Md. : 1950) 50 28877989
1993 Tyrosine-rich acidic matrix protein (TRAMP) accelerates collagen fibril formation in vitro. The Journal of biological chemistry 50 8103522
2002 Common HLA-B8-DR3 haplotype in Northern India is different from that found in Europe. Tissue antigens 49 12542740
2011 Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model. Cancer prevention research (Philadelphia, Pa.) 48 21911444
2003 Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. The Prostate 48 14518031
2015 Flavokawain A induces deNEDDylation and Skp2 degradation leading to inhibition of tumorigenesis and cancer progression in the TRAMP transgenic mouse model. Oncotarget 47 26497688
2005 Genotoxicity and oxidative stress of the mutagenic compounds formed in fumes of heated soybean oil, sunflower oil and lard. Toxicology in vitro : an international journal published in association with BIBRA 47 16216463
2013 Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing. Nucleic acids research 46 24097436
2000 Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3). FEBS letters 46 11094155
2017 Fish oil, lard and soybean oil differentially shape gut microbiota of middle-aged rats. Scientific reports 45 28400577
2016 Properties and oxidative stability of emulsions prepared with myofibrillar protein and lard diacylglycerols. Meat science 45 26775153
2022 NRF2 modulation in TRAMP mice: an in vivo model of prostate cancer. Molecular biology reports 42 36335520
2011 In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: involvement of Nrf2 and cell cycle/apoptosis signaling pathways. Molecular carcinogenesis 40 21837756
2015 The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases. Seminars in arthritis and rheumatism 39 25887448
2016 Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1. Chemical research in toxicology 38 26991801
1986 Altered phagocytosis by monocytes from HLA-DR2 and DR3-positive healthy adults is Fc gamma receptor specific. Journal of immunology (Baltimore, Md. : 1950) 38 3009607
2018 The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells. Molecular carcinogenesis 37 29247555
2012 Changes in glucose tolerance and leptin responsiveness of rats offered a choice of lard, sucrose, and chow. American journal of physiology. Regulatory, integrative and comparative physiology 37 22496363
2012 Tregs expanded in vivo by TNFRSF25 agonists promote cardiac allograft survival. Transplantation 37 22902792
2010 Dietary zinc and prostate cancer in the TRAMP mouse model. Journal of medicinal food 37 20136438
2016 A Novel Role for TL1A/DR3 in Protection against Intestinal Injury and Infection. Journal of immunology (Baltimore, Md. : 1950) 36 27233964
2013 Immunobiology of TNFSF15 and TNFRSF25. Immunologic research 35 24242819
2025 Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD. Gut 33 39266053
2020 Quercetin-Resveratrol Combination for Prostate Cancer Management in TRAMP Mice. Cancers 33 32748838
1999 Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: overlapping natural and artificial determinants in the human acetylcholine receptor. Journal of immunology (Baltimore, Md. : 1950) 33 10201931
1999 HLA associations in type 1 diabetes among patients not carrying high-risk DR3-DQ2 or DR4-DQ8 haplotypes. Tissue antigens 33 10674967
1992 The evolutionary origin of the HLA-DR3 haplotype. Immunogenetics 32 1541486
2020 Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo. Scientific reports 31 33097818
2014 High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice. The Prostate 30 25053105
2012 T cell costimulation by TNFR superfamily (TNFRSF)4 and TNFRSF25 in the context of vaccination. Journal of immunology (Baltimore, Md. : 1950) 30 22956587
2020 Substrate specificity of the TRAMP nuclear surveillance complexes. Nature communications 29 32561742
2016 Icaritin suppresses development of neuroendocrine differentiation of prostate cancer through inhibition of IL-6/STAT3 and Aurora kinase A pathways in TRAMP mice. Carcinogenesis 29 27207661
2009 HLA-DQ8 (DQB1*0302)-restricted Th17 cells exacerbate experimental autoimmune encephalomyelitis in HLA-DR3-transgenic mice. Journal of immunology (Baltimore, Md. : 1950) 29 19342694
1995 Primate DRB genes from the DR3 and DR8 haplotypes contain ERV9 LTR elements at identical positions. Immunogenetics 29 7806299
2011 Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer. Cancers 27 21961053
2022 Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2. The Journal of clinical endocrinology and metabolism 26 35665810
2016 Glutathione Peroxidase 3 Inhibits Prostate Tumorigenesis in TRAMP Mice. The Prostate 26 27325372
2012 A multistage-polyepitope vaccine protects against Mycobacterium tuberculosis infection in HLA-DR3 transgenic mice. Vaccine 26 23103299
2010 Mixed tocotrienols inhibit prostate carcinogenesis in TRAMP mice. Nutrition and cancer 25 20661828
2005 Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion. The European journal of neuroscience 24 15926921
2013 Immunization with cross-conserved H1N1 influenza CD4+ T-cell epitopes lowers viral burden in HLA DR3 transgenic mice. Human vaccines & immunotherapeutics 23 24045788
2012 TNFRSF25 agonistic antibody and galectin-9 combination therapy controls herpes simplex virus-induced immunoinflammatory lesions. Journal of virology 23 22811539
2012 Air proteins control differential TRAMP substrate specificity for nuclear RNA surveillance. RNA (New York, N.Y.) 23 22923767
2011 The Ron receptor promotes prostate tumor growth in the TRAMP mouse model. Oncogene 22 21625214
2008 HLA-DQ6 (DQB1*0601)-restricted T cells protect against experimental autoimmune encephalomyelitis in HLA-DR3.DQ6 double-transgenic mice by generating anti-inflammatory IFN-gamma. Journal of immunology (Baltimore, Md. : 1950) 21 18490779
2002 Derivation of MPR and TRAMP models of prostate cancer and prostate cancer metastasis for evaluation of therapeutic strategies. Urologic oncology 21 12474544
2019 Ultrasound-mediated interfacial protein adsorption and fat crystallization in cholesterol-reduced lard emulsion. Ultrasonics sonochemistry 20 31450308
2011 CD161 DEFINES EFFECTOR T CELLS THAT EXPRESS LIGHT AND RESPOND TO TL1A-DR3 SIGNALING. European journal of microbiology & immunology 20 22348196
2022 The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling. Allergy, asthma & immunology research 19 35255540
2020 Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves' disease. Journal of autoimmunity 19 31980336
2019 Activation of the DR3-TL1A Axis in Donor Mice Leads to Regulatory T Cell Expansion and Activation With Reduction in Graft-Versus-Host Disease. Frontiers in immunology 19 31379829
2017 Systemic alkalinisation delays prostate cancer cell progression in TRAMP mice. Journal of enzyme inhibition and medicinal chemistry 19 28095711
2007 Safingol toxicology after oral administration to TRAMP mice: demonstration of safingol uptake and metabolism by N-acylation and N-methylation. Drug and chemical toxicology 19 17613006
1988 Two variants of DRw52, DR3, and DQw2 specificities distinguish two different DR3-bearing extended haplotypes. Human immunology 19 2835344
2019 Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes. Diabetes 18 30962219
2020 Comparative study of dietary fat: lard and sugar as a better obesity and metabolic syndrome mice model. Archives of physiology and biochemistry 17 33176505
2018 Association of HLA-DR3 and HLA-DR15 Polymorphisms with Risk of Systemic Lupus Erythematosus. Chinese medical journal 17 30511687
2016 Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders. Immunopharmacology and immunotoxicology 17 26810853