Affinage

TNFRSF6B

Tumor necrosis factor receptor superfamily member 6B · UniProt O95407

Length
300 aa
Mass
32.7 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFRSF6B (DcR3/TR6) is a secreted decoy receptor of the TNF receptor superfamily that neutralizes three TNF-family ligands — FasL, LIGHT, and TL1A — thereby suppressing apoptosis, T cell costimulation, and proinflammatory signaling across diverse immune and tissue contexts (PMID:10318773, PMID:11408521, PMID:11911831). Crystal structures of DcR3 in complex with each of its three ligands reveal that it recognizes invariant backbone atoms and conserved side-chain features in the membrane-proximal region of TNF-family trimers, explaining its unusual multi-ligand promiscuity (PMID:21300286, PMID:25087510, PMID:27806260). Beyond ligand sequestration, DcR3 exerts non-decoy functions by engaging heparan sulfate proteoglycans on target cells, activating PKC-δ/JNK to induce dendritic cell apoptosis, promoting osteoclast differentiation via ERK/p38-dependent TNF-α release, polarizing macrophages/microglia toward an M2 phenotype, and inhibiting T cell chemotaxis through suppression of Cdc42/actin polymerization via LIGHT reverse signaling (PMID:18006694, PMID:15002040, PMID:28438208, PMID:14500635). In tumor contexts, DcR3 promotes epithelial–mesenchymal transition and migration through NF-κB and PI3K/AKT/β-catenin pathways, and its own transcription is regulated by NF-κB, TGFβ3–Smad–Sp1, TIPE/PI3K/AKT, ZNF37A promoter repression, and miR-340-mediated post-transcriptional silencing (PMID:28560426, PMID:30050309, PMID:31409774, PMID:39571490, PMID:29311025).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identification of DcR3/TR6 as a secreted (transmembrane domain-lacking) TNF receptor family member that binds both LIGHT and FasL established it as a soluble decoy receptor capable of competing with membrane-bound receptors for TNF-family ligands.

    Evidence Immunoprecipitation, flow cytometry with LIGHT-transfected cells, and cytotoxicity assay in HT29 cells

    PMID:10318773

    Open questions at the time
    • Affinity hierarchy among ligands not quantified
    • In vivo relevance of decoy function not yet demonstrated
  2. 2001 High

    Demonstration that DcR3 blocks FasL-induced hepatic apoptosis in vivo and competes with HVEM/LTβR for LIGHT on activated T cells to suppress alloimmune responses established its physiological role as an immunomodulatory decoy receptor.

    Evidence BIAcore binding, FasL-hepatitis mouse model rescue (PMID:11408521); flow cytometry competition, CTL assay, mouse heart allograft model (PMID:11390428)

    PMID:11390428 PMID:11408521

    Open questions at the time
    • Endogenous source and regulation of DcR3 secretion in vivo not defined
    • Relative contribution of FasL vs. LIGHT neutralization in disease models unclear
  3. 2002 High

    Discovery that TL1A is a third ligand for DcR3 expanded the decoy receptor's functional scope to include blockade of DR3-mediated NF-κB activation, apoptosis, and T cell costimulation.

    Evidence Ligand-receptor binding assay, NF-κB reporter, apoptosis assay, T cell costimulation assays

    PMID:11911831

    Open questions at the time
    • Structural basis for binding three distinct ligands unknown at this point
    • Hierarchy of ligand neutralization in vivo unclear
  4. 2003 High

    Elucidation of non-decoy functions: DcR3 inhibits T cell chemotaxis by suppressing Cdc42 activation, p38 MAPK, and actin polymerization through LIGHT reverse signaling, and proteolytic cleavage at R218-A219 differentially ablates FasL- but not LIGHT-binding, revealing functional modularity.

    Evidence Transwell chemotaxis, Cdc42/p38/actin assays, in vivo T cell trafficking (PMID:14500635); mass spectrometry, N-terminal sequencing, R218Q mutagenesis (PMID:12566095)

    PMID:12566095 PMID:14500635

    Open questions at the time
    • Protease identity responsible for R218 cleavage unknown
    • Whether reverse signaling operates through all three ligands not tested
  5. 2004 High

    DcR3 induces osteoclast differentiation from monocytes and macrophages via reverse signaling that activates ERK/p38 MAPK and TNF-α release, establishing a non-decoy effector function beyond immune suppression.

    Evidence Primary monocyte/RAW264.7/bone marrow differentiation, TRAP staining, bone resorption, TNFR-Fc blocking

    PMID:15002040

    Open questions at the time
    • Counter-receptor for reverse signaling on monocytes not identified
    • Relevance to bone pathology in vivo not established
  6. 2005 Medium

    Cell-surface-expressed DcR3 triggers reverse signaling through LIGHT and FasL on T cells to enhance costimulation and generate anti-tumor immunity, demonstrating that DcR3 can function bidirectionally depending on its presentation form.

    Evidence Engineered surface-TR6-expressing P815 tumor cells, T cell costimulation assay, in vivo tumor vaccine model

    PMID:15814697

    Open questions at the time
    • Whether soluble vs. membrane-tethered DcR3 triggers identical reverse signals not resolved
    • Single tumor model system
  7. 2007 High

    Identification of heparan sulfate proteoglycans as a non-ligand binding partner for DcR3 revealed a distinct HSPG-mediated mechanism by which DcR3 activates PKC-δ/JNK, upregulates DR5, and assembles a FADD-containing DISC to induce dendritic cell apoptosis.

    Evidence PKC-δ/JNK activation, DR5 upregulation, FADD co-IP (DISC formation), HBD-Fc domain mapping

    PMID:18006694

    Open questions at the time
    • Specific HSPG species mediating DC apoptosis not identified
    • Whether HSPG-mediated effects and ligand-decoy effects are independently regulated in vivo unknown
  8. 2009 High

    DcR3 was shown to protect islet β cells from cytokine-induced apoptosis via massive upregulation of Adcyap1 and downregulation of Bank1, and to suppress Th17 responses through FasL-dependent disruption of IL-6/IL-23 signaling, broadening its immunoregulatory scope.

    Evidence DcR3 transgenic mouse islet transplant, microarray, Adcyap1 overexpression/Bank1 knockdown rescue (PMID:20007581); DcR3-Fc on PLP-specific lymph node cells with FasL-deficient controls (PMID:19269042)

    PMID:19269042 PMID:20007581

    Open questions at the time
    • Direct transcriptional targets of DcR3-mediated signaling in β cells not mapped
    • In vivo relevance of Th17 suppression in autoimmune disease models limited
  9. 2011 High

    Crystal structures of DcR3 alone and complexed with TL1A revealed that DcR3 recognizes invariant backbone and conserved side-chain atoms in the membrane-proximal half of TNF ligands, providing the structural explanation for its unique multi-ligand promiscuity and employing antideterminants to exclude non-cognate TNF members.

    Evidence X-ray crystallography, site-directed mutagenesis, biochemical binding assays

    PMID:21300286

    Open questions at the time
    • Structures with LIGHT and FasL not yet available at this time
    • Dynamic aspects of binding not captured by crystallography
  10. 2014 High

    Crystal structures of LIGHT and the LIGHT:DcR3 complex, followed by the FasL:DcR3 structure, completed the structural picture for all three ligand complexes, confirming a unified recognition mechanism targeting invariant backbone functionalities across all TNF-family partners.

    Evidence X-ray crystallography with structure-based mutagenesis for LIGHT:DcR3 (PMID:25087510) and FasL:DcR3 (PMID:27806260)

    PMID:25087510 PMID:27806260

    Open questions at the time
    • No full-length DcR3 structure with post-translational modifications
    • Structural basis for HSPG binding remains undetermined
  11. 2015 High

    Phosphoproteomic analysis revealed that DcR3 suppresses macrophage activation during influenza infection by activating STK10, inactivating PKC-α, reducing ERK/JNK signaling, and downregulating TLR3/7, providing an unbiased signaling map of DcR3's anti-inflammatory effects.

    Evidence Phosphoproteomics, Western blot, DcR3-transgenic mouse influenza A model with reduced lethality

    PMID:25940317

    Open questions at the time
    • Direct receptor mediating these effects on macrophages (HSPG vs. ligand reverse signaling) not distinguished
    • Phosphoproteomic hits not individually validated by knockdown
  12. 2017 High

    DcR3 was shown to promote M2a microglial polarization via HSPG interaction and reduce amyloid pathology in APP transgenic mice, and to drive hepatoma migration through NF-κB-mediated E-cadherin loss, revealing context-dependent effector functions in neurodegeneration and cancer.

    Evidence APP/DcR3 double-transgenic mice, behavioral tests, microglial phenotyping (PMID:28438208); IκBα/p65 Western blot, migration assay in hepatoma (PMID:28560426)

    PMID:28438208 PMID:28560426

    Open questions at the time
    • Whether DcR3's neuroprotective effect is solely HSPG-dependent or involves ligand neutralization not fully resolved
    • Hepatoma findings lack in vivo validation
  13. 2018 Medium

    Transcriptional and post-transcriptional regulation of DcR3 was mapped: TGFβ3–Smad–Sp1 activates the DcR3 promoter in HCC, TIPE/PI3K/AKT promotes DcR3 transcription, miR-340 directly targets the DcR3 3′UTR, and ZNF37A represses the DcR3 promoter, with DcR3 knockdown restoring chemoradiosensitivity.

    Evidence Luciferase reporter assays for Smad-Sp1, miR-340, TIPE/PI3K/AKT, and ZNF37A at DcR3 promoter/3′UTR; knockdown rescue experiments [PMID:31409774, PMID:29311025, PMID:33718119, PMID:39571490]

    PMID:29311025 PMID:31409774 PMID:33718119 PMID:39571490

    Open questions at the time
    • Integration among multiple transcriptional inputs not modeled
    • Endogenous chromatin context for promoter regulation not confirmed by ChIP
    • miR-340 regulation validated in single cell line
  14. 2018 Medium

    DcR3 drives epithelial–mesenchymal transition in gastric and colorectal cancers through PI3K/AKT/GSK-3β/β-catenin and TGFβ3/SMAD signaling, promoting proliferation, migration, and metastasis in vivo.

    Evidence shRNA knockdown, Western blot of PI3K/AKT/GSK-3β/β-catenin and EMT markers in gastric cancer (PMID:30050309); overexpression/knockdown with xenograft/metastasis models in CRC (PMID:27764793)

    PMID:27764793 PMID:30050309

    Open questions at the time
    • Receptor through which DcR3 activates PI3K/AKT in tumor cells not identified
    • Whether EMT induction is decoy- or HSPG-dependent not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the receptor(s) mediating DcR3's HSPG-dependent non-decoy signaling, the structural basis for HSPG engagement, the protease(s) responsible for R218 cleavage, and whether the diverse downstream signaling pathways (PKC-δ/JNK, ERK/p38, PI3K/AKT, NF-κB, STK10) operate through a unified or cell-type-specific proximal mechanism.
  • No structure of DcR3 HSPG-binding domain with an HSPG ligand
  • Protease for R218 cleavage unidentified
  • Unified signaling model integrating decoy and non-decoy functions lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4
Partners
CD44FASLGSDC2TNFSF14TNFSF15

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TR6/DcR3 is a secreted TNF receptor family member (lacking transmembrane domain) that specifically binds two TNF family ligands, LIGHT and FasL, as demonstrated by immunoprecipitation and flow cytometry with LIGHT-transfected cells; binding to LIGHT inhibits LIGHT-mediated cytotoxicity in HT29 cells by competing with HVEM/TR2 and LTβR. Histidine-tag pulldown/immunoprecipitation, flow cytometry with transfected cells, cytotoxicity assay The Journal of biological chemistry High 10318773
2001 TR6/DcR3 binds FasL and blocks FasL-mediated apoptosis in vitro (hepatocytes, HT-29, Jurkat) and in vivo; TR6 can cross-react with membrane-bound murine FasL and pretreatment of mice with TR6 blocked FasL-induced lethal fulminant hepatic apoptosis, establishing its in vivo decoy receptor function against FasL. BIAcore binding assay, cell viability assays, in vivo FasL-hepatitis mouse model The Journal of pharmacology and experimental therapeutics High 11408521
2002 TL1A is a ligand for both DR3 and DcR3 (TR6); TL1A induces NF-κB activation and apoptosis in DR3-expressing cell lines, and TR6-Fc protein antagonizes these signaling events; TL1A acts as a T cell costimulator increasing IL-2 responsiveness and proinflammatory cytokine secretion, while TR6 opposes these effects. Ligand-receptor binding assay, NF-κB reporter assay, apoptosis assay, T cell costimulation assay in vitro and in vivo Immunity High 11911831
2001 TR6/DcR3-Fc binds human LIGHT on 293 cells and activated T cells, competing with the LIGHT receptor TR2; TR6-Fc downregulates CTL activity in vitro, modulates lymphokine production by alloantigen-stimulated T cells, and ameliorates graft-versus-host response and heart allograft rejection in mice. Flow cytometry competition binding, immunoprecipitation, in vitro CTL assay, mouse heart allograft transplant model The Journal of clinical investigation High 11390428
2003 TR6/DcR3 inhibits T cell chemotaxis toward CXCL12 in vitro and in vivo; mechanistically, TR6 pretreatment prevents Cdc42 activation, downstream p38 MAPK activation, actin polymerization, and pseudopodium formation in T cells, acting through LIGHT reverse signaling. Transwell chemotaxis assay, in vivo T cell trafficking, Cdc42 activation assay, p38 MAPK Western blot, actin polymerization assay Journal of immunology High 14500635
2003 TR6/DcR3 is secreted by PBMC upon mitogen stimulation and inhibits actin polymerization and pseudopodium formation in T cells, suppressing T cell aggregation induced by alloantigens, anti-CD3, or PHA, whether TR6 is in soluble or solid-phase form. PBMC stimulation, actin polymerization assay, T cell aggregation assay with solid-phase and soluble TR6-Fc Journal of cellular biochemistry Medium 12761893
2003 DcR3 is proteolytically cleaved between R218 and A219 in vivo (identified by mass spectrometry and N-terminal sequencing), generating fragment DcR3(1-218) that retains LIGHT-binding and LIGHT-blocking activity but loses FasL-binding and FasL-mediated apoptosis inhibition; engineering R218Q (FLINT) prevents cleavage and restores full dual activity. Mass spectrometry, N-terminal sequencing, in vitro and in vivo proteolytic stability assay, functional apoptosis and LIGHT-binding assays with engineered mutant Biochemical pharmacology High 12566095
2004 DcR3 induces osteoclast formation from human monocytes, murine RAW264.7 macrophages, and bone marrow cells via 'reverse signaling'; DcR3 treatment induces TNF-α release through ERK and p38 MAPK signaling pathways, and the osteoclastogenic effect is abrogated by TNFR-Fc. Primary monocyte and macrophage differentiation assay, TRAP staining, bone resorption assay, ERK/p38 MAPK Western blot, TNF-α ELISA, TNFR-Fc blocking Cell death and differentiation High 15002040
2007 DcR3 induces dendritic cell apoptosis by activating PKC-δ and JNK, upregulating DR5, and recruiting FADD to form a death-inducing signaling complex (DISC); the heparan sulfate proteoglycan (HSPG)-binding domain of DcR3 is responsible for this activity, as HBD-Fc fusion protein also triggers DC apoptosis via PKC-δ. PKC-δ and JNK activation assays, DR5 upregulation Western blot, FADD co-immunoprecipitation (DISC formation), HSPG-binding domain fusion protein assay Blood High 18006694
2011 Crystal structures of unliganded DcR3 ectodomain and its complex with TL1A reveal that DcR3 interacts with invariant backbone and conserved side-chain atoms in the membrane-proximal half of TL1A; complementary mutagenesis confirms that this mode of recognition of invariant features (supported by antideterminants excluding other TNF family members) is the structural basis for DcR3's ability to bind three distinct TNF ligands. X-ray crystallography, site-directed mutagenesis, biochemical binding assays Structure High 21300286
2014 Crystal structures of LIGHT and the LIGHT:DcR3 complex reveal the structural basis for DcR3-mediated neutralization of LIGHT; structure-based LIGHT mutants with altered affinities for DcR3 and HVEM were generated, mechanistically demonstrating the binding interface. X-ray crystallography, site-directed mutagenesis, binding affinity assays Structure High 25087510
2016 Crystal structure of FasL in complex with DcR3 reveals that DcR3 recognizes invariant main-chain and conserved side-chain functionalities of FasL (consistent with TL1A:DcR3 and LIGHT:DcR3 structures); recombinant FasL with native glycosylation or structure-inspired mutations has enhanced pro-apoptotic activity (reduced aggregation) efficiently inhibited by recombinant DcR3. X-ray crystallography, functional apoptosis assay with Jurkat cells, glycosylation and mutagenesis analysis Structure High 27806260
2009 DcR3 protects islet beta cells from cytokine-induced apoptosis via three pathways (FasL, LIGHT, and TL1A); DNA microarray revealed DcR3 upregulates Adcyap1 (>700-fold) and downregulates Bank1 (50-fold) in cytokine-assaulted transgenic islets; forced overexpression of Adcyap1 or knockdown of Bank1 in NIT-1 insulinoma cells independently protected from cytokine-triggered apoptosis. DcR3 transgenic mouse model, islet transplantation, DNA microarray, plasmid transfection (Adcyap1), siRNA knockdown (Bank1), apoptosis assay Journal of immunology High 20007581
2009 DcR3-Fc increases integrin α4 (VLA-4) expression in THP-1 macrophages, promotes macrophage aggregate formation, and inhibits cycloheximide-induced apoptosis; anti-VLA-4 antibody abrogates both the aggregate formation and anti-apoptotic effect of DcR3-Fc, demonstrating a non-decoy function mediated through integrin α4 upregulation. Flow cytometry (integrin α4 expression), morphology assay (aggregate formation), apoptosis assay, blocking antibody Biochemical and biophysical research communications Medium 19748482
2009 DcR3 suppresses Th17 immune responses by disrupting Fas-FasL interactions; treatment of PLP-specific lymph node cells with DcR3.Fc suppressed IL-17, reduced Th17 cell proportion, and decreased IL-6 and IL-23; DcR3.Fc treatment of CD4+ T cells with defective FasL did not influence IL-17 production, indicating FasL-dependent mechanism. Cytokine ELISA, flow cytometry (Th17 proportion), FasL-deficient T cell controls, encephalitogenicity assay Journal of neuroimmunology Medium 19269042
2010 DcR3 inhibits p53-dependent Fas-mediated apoptotic signaling to confer radioresistance; overexpression of Dcr3 in radiosensitive cells increased survival after γ-irradiation; knockdown abolished radioresistance; when p53 was introduced into p53-null H1299 cells, siDcr3 restored radiosensitivity via p53-dependent Fas pathway. Clonogenic survival assay, siRNA knockdown, p53 introduction (plasmid), Dcr3 overexpression, Western blot International journal of radiation biology Medium 20597837
2011 DcR3 binds TL1A expressed on rheumatoid synovial fibroblasts (RA-FLS), resulting in negative regulation of cytokine-induced cell proliferation; this DcR3-TL1A reverse signaling mechanism was blocked by anti-TL1A antibody, distinguishing it from DcR3's canonical decoy function. Cell proliferation assay, blocking antibody against FasL/LIGHT/TL1A, identification of TL1A as the relevant counter-receptor on RA-FLS International journal of molecular medicine Medium 21537832
2011 DcR3-Fc induces chondrocyte proliferation specifically via ERK signaling and Fas-L; DcR3-Fc increased phospho-ERK (not p38 or JNK), and this proliferative effect was blocked by MEK1/2 inhibitor PD098059 or by anti-FasL blocking antibody, showing FasL reverse signaling activates ERK to promote OA chondrocyte proliferation. WST proliferation assay, phospho-ERK/p38/JNK Western blot, MEK1/2 inhibitor, anti-FasL blocking antibody Osteoarthritis and cartilage Medium 21420502
2013 DcR3 mutations (T56I and H122Y) identified in SLE patients exhibit altered FasL-binding kinetics and significantly increase lymphocyte proliferation compared to wild-type protein, establishing that these gain-of-function mutations alter DcR3's regulatory activity. DNA sequencing, recombinant mutant protein production, FasL-binding kinetics assay, lymphocyte proliferation assay The Journal of rheumatology Medium 23729807
2015 DcR3 suppresses influenza A virus-induced macrophage activation; proteome-wide phosphoproteomic mapping revealed DcR3 activates STK10 (negative regulator of cell migration) and inactivates PKC-α, reducing ERK and JNK activation; DcR3 also downregulates TLR3 and TLR7 expression in macrophages; DcR3-transgenic mice show reduced pulmonary infiltration and lethality. Phosphoproteomic mapping, Western blot (ERK/JNK/PKC-α), TLR3/7 expression, DcR3-transgenic mouse IAV model, BALF cytokine measurement Journal of molecular medicine High 25940317
2017 DcR3 promotes hepatoma cell migration by inducing IκBα degradation and p65 nuclear translocation (NF-κB activation), leading to cytoskeleton remodeling and E-cadherin downregulation; immunofluorescence confirmed increased DcR3 and decreased E-cadherin in hepatoma cells, with opposite expression patterns in normal vs. cancerous liver tissue. IκBα/p65 Western blot, immunofluorescence, flow cytometry, immunohistochemistry, migration assay Oncology reports Medium 28560426
2017 DcR3 ameliorates amyloid-β-induced memory deficits and reduces amyloid plaque in APP transgenic mice by interacting with heparan sulfate proteoglycans and activating IL-4+YM1+ M2a-like microglia, reducing proinflammatory cytokines and promoting microglial phagocytosis. APP/DcR3 double-transgenic mice, Morris water maze, fear conditioning, immunostaining, ELISA, Q-PCR, immunoprecipitation (DcR3-HSPG interaction), in vitro cytokine and phagocytosis assays Molecular neurodegeneration High 28438208
2018 DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells by activating the PI3K/AKT/GSK-3β/β-catenin signaling pathway; DcR3 knockdown reduces p-AKT, p-GSK-3β, and β-catenin, increases E-cadherin, and decreases N-cadherin and Vimentin. shRNA knockdown, Western blot (PI3K/AKT/GSK-3β/β-catenin pathway), cell proliferation, invasion, migration, and EMT marker assays OncoTargets and therapy Medium 30050309
2019 DcR3 expression in HCC is regulated by the TGFβ3-Smad-Sp1 signaling pathway, which directly targets DcR3 promoter regions; overexpression of DcR3 promotes Th2 and Treg differentiation while inhibiting Th1, and DcR3 knockdown restores CD4+ T cell immunity. Promoter analysis, luciferase reporter assay (Smad-Sp1 at DcR3 promoter), T cell differentiation assay, cytokine profiling Oncogenesis Medium 31409774
2019 DcR3 promotes pancreatic cancer proliferation and invasion via a positive feedback loop: DcR3 promotes STAT1 phosphorylation → IRF1 upregulation → IRF1 increases DcR3 transcription; IRF1 also upregulates CEACAM1 downstream of DcR3. Loss- and gain-of-function experiments, Western blot (p-STAT1, IRF1), transcriptional reporter assay, in vitro invasion/migration, in vivo tumor growth American journal of cancer research Medium 31911850
2018 DcR3 is directly transcriptionally regulated by miR-340, which targets the DcR3 3'UTR (validated by luciferase assay); miR-340 overexpression reduces DcR3 expression and downstream TGF-β1/Smad2 signaling (including Smad2 phosphorylation), promoting apoptosis and blocking proliferation of HepG2 HCC cells. Luciferase reporter assay (DcR3 3'UTR), miR-340 mimic transfection, Western blot (DcR3, TGF-β1, p-Smad2), apoptosis and proliferation assays Digestive and liver disease Medium 29311025
2016 DcR3 promotes EMT in colorectal cancer cells through TGF-β3/SMAD signaling; DcR3 overexpression enhances CRC proliferation and migration in vitro and tumorigenesis/metastasis in vivo, while DcR3 knockdown suppresses these effects; cooperation between DcR3 and TGF-β3/SMAD-EMT signaling correlates with survival. DcR3 overexpression and knockdown, in vitro proliferation/migration assays, in vivo tumor xenograft and metastasis models, Western blot (SMAD pathway), immunohistochemistry Oncotarget Medium 27764793
2024 DcR3 expression in HUVECs is upregulated by microbial toxins (LPS, LTA, zymosan) via the NF-κB signaling pathway; NF-κB inhibitor PDTC decreased DcR3 expression while JNK (SP600125) and p38 MAPK (SB203580) inhibitors had no effect, placing DcR3 induction specifically downstream of NF-κB. RT-PCR, ELISA, pathway inhibitor experiments (PDTC, SP600125, SB203580) in HUVECs and Jurkat cells BMC biochemistry Medium 30587127
2024 ZNF37A binds the TNFRSF6B (DcR3) promoter region, suppressing its transcriptional activity; ZNF37A downregulation leads to chemoradiation resistance in colorectal cancer by increasing TNFRSF6B expression and inhibiting apoptosis; TNFRSF6B knockdown restores CRC sensitivity to chemoradiotherapy. Genome-wide expression profiling, molecular biology validation, TNFRSF6B promoter binding by ZNF37A (demonstrated functionally), shRNA knockdown, clinical patient cohort validation Translational oncology Medium 39571490
2021 TIPE (TNF-α-induced protein 8) regulates DcR3 expression by activating the PI3K/AKT signaling pathway; TIPE overexpression enhanced DcR3 promoter transcriptional activity (dual-luciferase assay), increased DcR3 secretion, and PI3K/AKT inhibitors blocked this effect. Dual-luciferase reporter assay (DcR3 promoter), TIPE overexpression/knockdown, PI3K/AKT inhibitors, ELISA (DcR3 secretion), proliferation and apoptosis assays Frontiers in oncology Medium 33718119
2008 DcR3 binds ovarian cancer cells (EOC) via heparan sulfate proteoglycans (HSPGs; Syndecans-2 and CD44v3); DcR3 binding was inhibited by heparin and heparinase; after DcR3 binding, cells alter BRCA1 expression and platinum sensitivity, with the direction of effect dependent on which HSPGs are present on the cell surface. DcR3 binding assay with heparin/heparinase competition, flow cytometry, HSPG expression profiling, PCR array, RT-PCR, Western blot (BRCA1), platinum cytotoxicity assay BMC cancer Medium 22583667
2005 Cell surface-expressed TR6/DcR3 triggers reverse signaling through LIGHT and FasL on T cells, enhancing T cell costimulation (proliferation, IL-2 and IFN-γ secretion); TR6-expressing tumor cells (TR6-P815) have reduced tumorigenicity, and inactivated TR6-P815 cells function as a tumor vaccine protecting mice from parental tumor challenge and eliminating established tumors. Cell surface TR6 expression engineering, T cell costimulation assay (proliferation, cytokine secretion), tumor challenge/vaccine in vivo mouse model Journal of immunology Medium 15814697

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
1999 A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. The Journal of biological chemistry 304 10318773
2000 Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proceedings of the National Academy of Sciences of the United States of America 187 10655513
2001 Modulation of T-cell responses to alloantigens by TR6/DcR3. The Journal of clinical investigation 104 11390428
2008 Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis. Clinical immunology (Orlando, Fla.) 95 18757243
2010 High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis. Clinical immunology (Orlando, Fla.) 78 20675196
2003 Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients. International journal of cancer 74 12740925
2011 Upregulation and nuclear localization of TNF-like cytokine 1A (TL1A) and its receptors DR3 and DcR3 in psoriatic skin lesions. Experimental dermatology 72 21672030
2000 Amplification and expression of a decoy receptor for fas ligand (DcR3) in virus (EBV or HTLV-I) associated lymphomas. Cancer letters 68 11098089
2004 Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells. Cell death and differentiation 65 15002040
2007 Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3). Blood 62 18006694
2003 Death decoy receptor TR6/DcR3 inhibits T cell chemotaxis in vitro and in vivo. Journal of immunology (Baltimore, Md. : 1950) 56 14500635
2011 Decoy strategies: the structure of TL1A:DcR3 complex. Structure (London, England : 1993) 54 21300286
2004 Quantification and detection of DcR3, a decoy receptor in TNFR family. Journal of immunological methods 51 14871535
2011 Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 46 21978578
2000 Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients. Clinical and experimental immunology 46 10632670
2015 Tumor Necrosis Factor-like Cytokine TL1A and Its Receptors DR3 and DcR3: Important New Factors in Mucosal Homeostasis and Inflammation. Inflammatory bowel diseases 45 26099067
2015 The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases. Seminars in arthritis and rheumatism 39 25887448
2001 In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor. The Journal of pharmacology and experimental therapeutics 39 11408521
2018 DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3β/β-catenin signaling pathway. OncoTargets and therapy 36 30050309
2016 Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure (London, England : 1993) 36 27806260
2009 DcR3 and survivin are highly expressed in colorectal carcinoma and closely correlated to its clinicopathologic parameters. Journal of Zhejiang University. Science. B 35 19735100
2014 Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly. Structure (London, England : 1993) 31 25087510
2008 Ascites from epithelial ovarian cancer contain high levels of functional decoy receptor 3 (DcR3) and is associated with platinum resistance. Gynecologic oncology 29 18723214
2009 The Decoy Receptor 3 (DcR3, TNFRSF6B) suppresses Th17 immune responses and is abundant in human cerebrospinal fluid. Journal of neuroimmunology 28 19269042
2004 Soluble receptor (DcR3) and cellular inhibitor of apoptosis-2 (cIAP-2) protect human cytotrophoblast cells against LIGHT-mediated apoptosis. The American journal of pathology 28 15215185
2017 Amelioration of amyloid-β-induced deficits by DcR3 in an Alzheimer's disease model. Molecular neurodegeneration 27 28438208
2002 DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer. International journal of cancer 27 12397645
2001 Ultraviolet light (UV) regulation of the TNF family decoy receptors DcR2 and DcR3 in human keratinocytes. Journal of cutaneous medicine and surgery 26 11907838
2012 DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1. BMC cancer 23 22583667
2008 IL5RA and TNFRSF6B gene variants are associated with sporadic IgA nephropathy. Journal of the American Society of Nephrology : JASN 23 18256354
2003 Decoy receptor 3 (DcR3) is proteolytically processed to a metabolic fragment having differential activities against Fas ligand and LIGHT. Biochemical pharmacology 23 12566095
2012 Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis. Diagnostic microbiology and infectious disease 22 22647538
2011 DcR3 induces cell proliferation through MAPK signaling in chondrocytes of osteoarthritis. Osteoarthritis and cartilage 22 21420502
2003 DcR3/TR6 effectively prevents islet primary nonfunction after transplantation. Diabetes 22 12941767
2016 DcR3, TFF3, and Midkine Are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors. Neuroendocrinology 21 27829249
2010 TNFRSF6B neutralization antibody inhibits proliferation and induces apoptosis in hepatocellular carcinoma cell. Pathology, research and practice 21 20591579
2007 Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. Cellular & molecular immunology 21 18163957
2019 Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma. Oncogenesis 20 31409774
2011 DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts. International journal of molecular medicine 20 21537832
2003 DcR3/TR6 modulates immune cell interactions. Journal of cellular biochemistry 20 12761893
2012 Significance of decoy receptor 3 (Dcr3) and external-signal regulated kinase 1/2 (Erk1/2) in gastric cancer. BMC immunology 19 22672288
2017 Downregulation of DcR3 sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis. OncoTargets and therapy 18 28176915
2014 Overexpression of DcR3 and its significance on tumor cell differentiation and proliferation in glioma. TheScientificWorldJournal 18 24741354
2010 Dcr3 inhibit p53-dependent apoptosis in gamma-irradiated lung cancer cells. International journal of radiation biology 18 20597837
2016 Expression and clinicopathological implication of DcR3 in lung cancer tissues: a tissue microarray study with 365 cases. OncoTargets and therapy 17 27570459
2010 Evidence of epistasis between TNFRSF14 and TNFRSF6B polymorphisms in patients with rheumatoid arthritis. Arthritis and rheumatism 17 20187130
2019 DcR3 promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop. American journal of cancer research 16 31911850
2017 DcR3 promotes hepatoma cell migration by downregulating E-cadherin expression. Oncology reports 16 28560426
2016 DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC. Oncotarget 16 27764793
2013 DcR3 regulates the growth and metastatic potential of SW480 colon cancer cells. Oncology reports 16 24101127
2008 High DcR3 expression predicts stage pN2-3 in gastric cancer. American journal of clinical oncology 16 18376232
2008 DcR3 as a diagnostic parameter and risk factor for systemic lupus erythematosus. International immunology 16 18562337
2003 Characterization of chicken TNFR superfamily decoy receptors, DcR3 and osteoprotegerin. Biochemical and biophysical research communications 16 12878204
2023 A novel promising laccase from the psychrotolerant and halotolerant Antarctic marine Halomonas sp. M68 strain. Frontiers in microbiology 15 36846806
2009 DcR3 protects THP-1 macrophages from apoptosis by increasing integrin alpha4. Biochemical and biophysical research communications 15 19748482
2009 DcR3 protects islet beta cells from apoptosis through modulating Adcyap1 and Bank1 expression. Journal of immunology (Baltimore, Md. : 1950) 15 20007581
2017 Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro. World journal of gastroenterology 14 28223726
2015 DcR3 suppresses influenza virus-induced macrophage activation and attenuates pulmonary inflammation and lethality. Journal of molecular medicine (Berlin, Germany) 14 25940317
2016 Decoy Receptor 3 (DcR3) as a Biomarker of Tumor Deterioration in Female Reproductive Cancers: A Meta-Analysis. Medical science monitor : international medical journal of experimental and clinical research 13 27246752
2013 Expression of TNFRSF6B in kidneys is a novel predictor for progression of chronic kidney disease. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 23449012
2013 Silencing of decoy receptor 3 (DcR3) expression by siRNA in pancreatic carcinoma cells induces Fas ligand-mediated apoptosis in vitro and in vivo. International journal of molecular medicine 13 23846297
2011 Expression of death decoy receptor-3 (DcR3) in human breast cancer and its functional effects on breast cancer cells in vitro. Journal of experimental therapeutics & oncology 13 21699018
2022 The Role of Decoy Receptor DcR3 in Gastrointestinal Malignancy. Cancer diagnosis & prognosis 12 35813013
2013 'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells. International journal of oncology 12 23817777
2013 MMP-2 and DcR3 expression in esophageal cancer tissue and correlation with patient survival. International journal of clinical and experimental medicine 12 24040480
2018 The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells. Experimental and therapeutic medicine 11 29725377
2018 Anti-oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient-derived tumor xenograft model. Head & neck 11 30537218
2017 Effects of miR-340 on hepatocellular carcinoma by targeting the DcR3 gene. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 11 29311025
2024 Protective effects of DcR3-SUMO on lipopolysaccharide-induced inflammatory cells and septic mice. International journal of biological macromolecules 10 38986982
2016 Effect of DcR3-specific siRNA on cell growth suppression and apoptosis induction in glioma cells via affecting ERK and AKT. OncoTargets and therapy 10 27621648
2015 Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS. Journal of cellular and molecular medicine 10 25823874
2012 Clinical significance of expression and amplification of the DcR3 gene in pancreatic carcinomas. Asian Pacific journal of cancer prevention : APJCP 10 22524850
2009 Expressions of Fas/DcR3 and RGD-FasL mediated apoptosis in pituitary adenomas. Neurology India 10 19305072
2021 TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC. Frontiers in oncology 9 33718119
2007 High DcR3 expression predicts stage pN2 in gastric cancer. Hepato-gastroenterology 8 18251184
2023 Research Progress of DcR3 in the Diagnosis and Treatment of Sepsis. International journal of molecular sciences 7 37629097
2016 Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2. Oncology letters 7 26998086
2014 Overexpression and clinicopathological contribution of DcR3 in bladder urothelial carcinoma tissues. Asian Pacific journal of cancer prevention : APJCP 7 25422191
2003 Pharmacokinetics, metabolic stability, and subcutaneous bioavailability of a genetically engineered analog of DcR3, FLINT [DcR3(R218Q)], in cynomolgus monkeys and mice. Drug metabolism and disposition: the biological fate of chemicals 7 12642478
2021 Serum decoy receptor 3 (DcR3): a promising biomarker for atopic asthma in children. Immunologic research 6 34383195
2019 Low plasma levels of decoy receptor 3 (DcR3) in the third trimester of pregnancy with preeclampsia. Taiwanese journal of obstetrics & gynecology 6 31122523
2015 Effect of TNFRSF6B neutralization antibody on cell growth suppression and apoptosis induction in glioma cells. Neoplasma 6 25997959
2007 Molecular cloning and preliminary expression analysis of banded dogfish (Triakis scyllia) TNF decoy receptor 3 (TNFRSF6B). Fish & shellfish immunology 6 18201904
2005 Tumor vaccine based on cell surface expression of DcR3/TR6. Journal of immunology (Baltimore, Md. : 1950) 6 15814697
2024 Dual Responsive Magnetic DCR3 Nanoparticles: A New Strategy for Efficiently Targeting Hepatocellular Carcinoma. Small (Weinheim an der Bergstrasse, Germany) 5 39604254
2021 The Network of Pro-Inflammatory Factors CD147, DcR3, and IL33 in the Development of Kawasaki Disease. Journal of inflammation research 5 34824540
2019 When Cultures Fail: Postmortem Decoy Receptor 3 (DcR3) as a Marker of Antemortem Sepsis. Academic forensic pathology 5 34394787
2018 Up-regulation of DcR3 in microbial toxins-stimulated HUVECs involves NF-κB signalling. BMC biochemistry 5 30587127
2017 Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3-associated signaling pathways. Oncotarget 5 29552282
2014 Promotive Effects of Dcr3 Gene on the Occurrence and Progression of Gastric Cancer and its Mechanism. Hepato-gastroenterology 5 26176090
2011 Expression of DcR3 and its effects in kaposi's sarcoma-associated herpesvirus-infected human endothelial cells. Intervirology 5 21293109
2010 Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation. Vaccine 5 20969926
2019 Association of Tumor Necrosis Like factor 1 A (TL1A) and its Decoy Receptor (DcR3) with The Disease Activity and Autoantibody Production in Rheumatoid Arthritis Patients. The Egyptian journal of immunology 4 31332995
2016 DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women. Oncotarget 4 27517320
2013 DcR3 mutations in patients with juvenile-onset systemic lupus erythematosus lead to enhanced lymphocyte proliferation. The Journal of rheumatology 4 23729807
2024 ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients. Translational oncology 3 39571490
2021 Integrative analysis of TNFRSF6B as a potential therapeutic target for pancreatic cancer. Journal of gastrointestinal oncology 3 34532119
2017 DcR3 combined with hematological traits serves as a valuable biomarker for the diagnosis of cancer metastasis. Oncotarget 3 29296192
2012 High serum DcR3 levels are associated with the occurrence of peritonitis in patients receiving chronic peritoneal dialysis. Journal of the Chinese Medical Association : JCMA 3 23245480