Affinage

TNFRSF6B

Tumor necrosis factor receptor superfamily member 6B · UniProt O95407

Length
300 aa
Mass
32.7 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFRSF6B (DcR3/TR6) is a secreted soluble decoy receptor of the TNF receptor superfamily that neutralizes three TNF-family ligands—FasL/CD95L, LIGHT, and TL1A—to dampen apoptosis, cytotoxic T-cell activity, and inflammatory signaling (PMID:10318773, PMID:11911831, PMID:11390428, PMID:11408521). Crystal structures of DcR3 bound to TL1A, LIGHT, and FasL show that it engages invariant main-chain and conserved side-chain atoms in the membrane-proximal half of each ligand, a single shared interface that explains its broad specificity while antideterminants exclude other TNF superfamily members (PMID:21300286, PMID:25087510, PMID:27806260); in functional terms this lets DcR3-Fc competitively block LIGHT binding to HVEM/TR2 and LTβR, antagonize TL1A-induced NF-κB activation and DR3 apoptosis, and inhibit FasL-mediated killing in vitro and in vivo (PMID:10318773, PMID:11911831, PMID:11408521). Proteolytic cleavage between R218 and A219 yields a fragment that retains LIGHT binding but loses FasL binding, and the R218Q (FLINT) substitution blocks cleavage to preserve activity against both ligands (PMID:12566095). Beyond decoy function, DcR3 acts as a ligand that engages heparan sulfate proteoglycans on target cells to trigger 'reverse signaling': HSPG cross-linking by its heparin-binding domain activates PKC-δ/JNK to upregulate DR5 and assemble a FADD-containing DISC in dendritic cells, drives ERK/p38-dependent TNF-α release to promote osteoclastogenesis in monocytes, and modulates macrophage and microglial activation (PMID:15002040, PMID:18006694, PMID:25940317, PMID:28438208). In T cells DcR3/LIGHT reverse signaling blocks Cdc42 activation, p38 phosphorylation, and actin polymerization to suppress chemotaxis and aggregation (PMID:14500635, PMID:12761893). In cancer, DcR3 promotes proliferation, migration, and EMT through PI3K/AKT/GSK-3β/β-catenin, TGF-β3/SMAD, and a self-reinforcing STAT1/IRF1 loop, and its own expression is controlled by NF-κB, TGFβ3-Smad-Sp1, and transcriptional repression by ZNF37A (PMID:30050309, PMID:27764793, PMID:31911850, PMID:31409774, PMID:30587127, PMID:39571490). Gain-of-function DcR3 missense mutations (T56I, H122Y) with altered FasL binding and increased lymphocyte proliferation have been identified in SLE patients (PMID:23729807).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established DcR3 as a soluble decoy that binds TNF-family ligands rather than transducing signal, by showing it captures LIGHT and FasL and neutralizes LIGHT cytotoxicity.

    Evidence Immunoprecipitation, flow cytometry on LIGHT-transfected cells, and cytotoxicity blockade in HT29 cells

    PMID:10318773

    Open questions at the time
    • Did not resolve the structural basis of multi-ligand recognition
    • TL1A not yet identified as a ligand
  2. 2001 High

    Defined the competitive mechanism against LIGHT and FasL and demonstrated immunological consequences, showing DcR3 displaces LIGHT from TR2 and blocks FasL-induced killing in vivo.

    Evidence Flow cytometry/IP competition with TR2, BIAcore SPR for FasL binding, CTL assays, and mouse GvHD and fulminant hepatitis models

    PMID:11390428 PMID:11408521

    Open questions at the time
    • Atomic interface not yet defined
    • Whether one binding site accommodates all ligands unknown
  3. 2002 High

    Identified TL1A as a third DcR3 ligand and showed DcR3-Fc antagonizes TL1A-driven NF-κB and apoptosis via the DR3 axis, expanding the decoy's ligand repertoire.

    Evidence Ligand binding, NF-κB reporter and apoptosis assays with TR6-Fc competition in DR3-expressing lines

    PMID:11911831

    Open questions at the time
    • Did not address reverse signaling through TL1A on ligand-bearing cells
  4. 2003 High

    Revealed that proteolytic cleavage at R218-A219 differentially abolishes FasL but not LIGHT binding, and that the R218Q mutation stabilizes the intact, dually active molecule—pharmacologically relevant for the FLINT therapeutic.

    Evidence Mass spectrometry, N-terminal sequencing, mutagenesis rescue, and in vivo pharmacokinetics

    PMID:12566095

    Open questions at the time
    • Identity of the responsible protease not established
    • Physiological context regulating cleavage unknown
  5. 2003 High

    Established that DcR3 acts as a ligand triggering reverse signaling in T cells, suppressing chemotaxis and aggregation by blocking Cdc42, p38, and actin polymerization.

    Evidence Transwell chemotaxis, Cdc42 activation, p38 phosphorylation, actin polymerization assays with anti-LIGHT mAb and in vivo chemotaxis model

    PMID:12761893 PMID:14500635

    Open questions at the time
    • Receptor on T cells mediating reverse signaling not fully defined
    • Link between LIGHT engagement and Cdc42 inhibition incomplete
  6. 2007 High

    Defined HSPG cross-linking by the heparin-binding domain as a decoy-independent mechanism, showing DcR3 induces DC apoptosis via PKC-δ/JNK, DR5 upregulation, and FADD-DISC formation.

    Evidence DISC co-IP, signaling Western blots, and HBD.Fc domain-dissection apoptosis assays

    PMID:18006694

    Open questions at the time
    • Specific HSPG species engaged in DCs not identified
    • How HSPG binding activates PKC-δ mechanistically unresolved
  7. 2004 Medium

    Showed DcR3 reverse signaling drives osteoclastogenesis, placing ERK/p38-induced TNF-α as the downstream effector of monocyte differentiation.

    Evidence Differentiation and bone resorption assays, MAPK Western blots, and TNFR-Fc blockade

    PMID:15002040

    Open questions at the time
    • Receptor coupling ERK/p38 to TNF-α not defined
    • Single lab
  8. 2009 Medium

    Extended DcR3 cytoprotection to islet, macrophage, and Th17 contexts, identifying distinct effectors (Adcyap1/Bank1, α4 integrin) and confirming FasL-dependence of IL-17 suppression.

    Evidence Transgenic islet microarray with siRNA/overexpression validation, anti-VLA4 blocking in macrophages, and FasL-defective T-cell controls

    PMID:19269042 PMID:19748482 PMID:20007581

    Open questions at the time
    • Whether effects are decoy- vs HSPG-mediated varies by context
    • Downstream mediators validated in single systems
  9. 2011 High

    Provided the atomic explanation for broad ligand specificity, showing a single membrane-proximal interface recognizes invariant backbone features of TL1A, FasL, and LIGHT.

    Evidence X-ray crystallography of unliganded DcR3 and the TL1A complex with mutagenesis and binding validation

    PMID:21300286

    Open questions at the time
    • FasL and LIGHT complexes not yet crystallized at this stage
    • Structural basis of HSPG/reverse signaling not addressed
  10. 2011 Medium

    Demonstrated context-specific proliferative reverse signaling, with DcR3-FasL engagement driving chondrocyte and synovial fibroblast responses through ERK.

    Evidence Proliferation assays with MEK inhibitor and ligand-blocking antibodies (anti-FasL vs anti-LIGHT/TL1A), and binding assays in RA-FLS

    PMID:21420502 PMID:21537832

    Open questions at the time
    • RA-FLS finding is Low-confidence/proliferation only
    • Reconciliation of pro-proliferative vs pro-apoptotic reverse signaling unresolved
  11. 2014 High

    Completed the structural recognition picture for LIGHT, showing how DcR3 blocks LIGHT engagement of HVEM and LTβR via structure-guided affinity mutants.

    Evidence X-ray crystallography of LIGHT and the LIGHT:DcR3 complex with mutagenesis

    PMID:25087510

    Open questions at the time
    • Functional consequences of designed mutants in vivo not tested
  12. 2016 High

    Confirmed the FasL:DcR3 interface conforms to the shared recognition paradigm, unifying the structural basis across all three ligands.

    Evidence X-ray crystallography of the FasL:DcR3 complex with Jurkat apoptosis inhibition

    PMID:27806260

    Open questions at the time
    • Does not address oligomeric stoichiometry on cell surfaces
  13. 2017 Medium

    Mapped HSPG-dependent reverse signaling onto innate immune restraint, showing DcR3 inactivates PKC-α and activates STK10 to suppress ERK/JNK and limit macrophage and microglial inflammation.

    Evidence Phosphoproteomic mapping, signaling Western blots, DcR3 transgenic mice, HBD.Fc domain experiments, and co-IP of DcR3-HSPG in brain

    PMID:25940317 PMID:28438208

    Open questions at the time
    • Specific HSPG receptor coupling to STK10 not defined
    • Single lab for each disease model
  14. 2019 Medium

    Established DcR3 as a pro-tumorigenic effector engaging PI3K/AKT/β-catenin, TGF-β3/SMAD, and a STAT1/IRF1 feedback loop to drive EMT, proliferation, and immune escape across multiple cancers.

    Evidence shRNA knockdown and overexpression with pathway Western blots, transcriptional reporters, T-cell differentiation assays, and xenograft models

    PMID:20597837 PMID:27764793 PMID:30050309 PMID:31409774 PMID:31911850

    Open questions at the time
    • Whether these cancer pathways require ligand decoy vs HSPG engagement is unclear
    • Each pathway shown in a single tumor type
  15. 2024 Medium

    Defined transcriptional control of DcR3, identifying inflammatory NF-κB induction and ZNF37A-mediated promoter repression as upstream regulators relevant to chemoradiation resistance.

    Evidence Selective pathway inhibitors in HUVECs, promoter binding/transcription assays, and shRNA knockdown rescue in colorectal cancer cells

    PMID:30587127 PMID:39571490

    Open questions at the time
    • Interplay between NF-κB, TGFβ3-Smad-Sp1, and ZNF37A on the promoter not integrated
    • ZNF37A regulation tested in single tumor context
  16. 2013 Medium

    Linked DcR3 dysfunction to autoimmunity, showing patient-derived gain-of-function mutations alter FasL binding kinetics and amplify lymphocyte proliferation.

    Evidence Patient DNA sequencing with recombinant mutant protein binding kinetics and lymphocyte proliferation assays

    PMID:23729807

    Open questions at the time
    • Small sample size
    • Causal contribution to SLE pathogenesis in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which HSPG receptors and adaptors physically couple DcR3 HSPG engagement to the divergent reverse-signaling outputs (apoptotic vs proliferative vs migration-suppressive) across cell types.
  • No defined transmembrane signaling partner for HSPG-mediated reverse signaling
  • Determinants selecting between opposing reverse-signaling outcomes unknown
  • Protease responsible for R218-A219 cleavage unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140313 molecular sequestering activity 5 GO:0048018 receptor ligand activity 4 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-168256 Immune System 4
Partners
CD44FASLGHSPG2ITGA4SDC2STK10TNFSF14TNFSF15

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TR6/DcR3 specifically binds two TNF-family ligands, LIGHT and FasL/CD95L, as demonstrated by immunoprecipitation with histidine-tagged recombinant TR6 and confirmed by flow cytometry on LIGHT-transfected HEK 293 EBNA cells. TR6 inhibits LIGHT-induced cytotoxicity in HT29 cells by blocking LIGHT interactions with HVEM/TR2 and LTβR. Immunoprecipitation, flow cytometry, cytotoxicity assay The Journal of biological chemistry High 10318773
2002 TL1A is a third ligand for DcR3/TR6 (and for signaling receptor DR3). TR6-Fc protein binds TL1A and antagonizes TL1A-induced NF-κB activation and apoptosis in DR3-expressing cell lines, demonstrating DcR3 decoy function against TL1A. Ligand binding assay, NF-κB reporter assay, apoptosis assay, TR6-Fc competition Immunity High 11911831
2001 TR6-Fc recombinant protein binds human LIGHT expressed on 293 cells or activated T cells and competes with the LIGHT receptor TR2 for LIGHT binding, as shown by flow cytometry and immunoprecipitation. TR6 downregulates CTL activity and modulates lymphokine production in vitro and in vivo. Flow cytometry, immunoprecipitation, CTL assay, graft-versus-host mouse model The Journal of clinical investigation High 11390428
2001 TR6 binds FasL and blocks FasL-mediated cell killing in vitro in multiple cell systems (human hepatocytes, HT-29, Jurkat cells) and in vivo in a mouse fulminant hepatitis model where pretreatment with TR6 blocked FasL-induced mortality. Human TR6 cross-reacts with membrane-bound mouse FasL. Binding of human TR6 to human FasL was confirmed by BIAcore surface plasmon resonance. BIAcore binding assay, cytotoxicity assays, in vivo mouse hepatitis model The Journal of pharmacology and experimental therapeutics High 11408521
2011 Crystal structure of unliganded DcR3 ectodomain and its complex with TL1A reveals that DcR3 interacts with invariant backbone and side-chain atoms in the membrane-proximal half of TL1A. Mutagenesis and biochemical studies show that the same interface supports recognition of FasL, LIGHT, and TL1A, while antideterminant features prevent binding to other TNF superfamily members. This is a unique mode of TNF:TNFR interaction enabling broad ligand specificity. X-ray crystallography, site-directed mutagenesis, biochemical binding assays Structure High 21300286
2014 Crystal structure of LIGHT and the LIGHT:DcR3 complex reveals the structural basis for DcR3-mediated neutralization of LIGHT and its inhibition of LIGHT interactions with HVEM and LTβR. Structure-guided LIGHT mutants with altered affinities for DcR3 and HVEM were generated, validating 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 the recognition paradigm seen in TL1A:DcR3 and LIGHT:DcR3 structures. Recombinant DcR3 efficiently inhibits FasL-induced Jurkat cell apoptosis. X-ray crystallography, apoptosis assay Structure High 27806260
2003 DcR3 is proteolytically cleaved between R218 and A219 (identified by mass spectrometry and N-terminal sequencing) to yield DcR3(1–218), which retains LIGHT-binding activity but loses FasL-binding ability. Engineering of R218Q substitution (FLINT/LY498919) prevents proteolytic cleavage and restores activity against both FasL and LIGHT in vitro and in vivo. Mass spectrometry, N-terminal sequencing, in vitro binding assay, site-directed mutagenesis, in vivo pharmacokinetic study Biochemical pharmacology High 12566095
2004 DcR3 induces osteoclast formation from human monocytes, murine RAW264.7 macrophages, and bone marrow cells via 'reverse signaling'. DcR3-differentiated cells exhibit osteoclast characteristics (polynuclear morphology, bone resorption, TRAP, CD51/61, MMP-9). DcR3 treatment induces TNF-α release through ERK and p38 MAPK signaling; the osteoclastogenic effect is abrogated by TNFR-Fc, confirming TNF-α as the downstream mediator. Cell differentiation assay, bone resorption assay, Western blotting for MAPK signaling, TNFR-Fc blocking experiment Cell death and differentiation Medium 15002040
2007 DcR3 induces apoptosis in dendritic cells by binding heparan sulfate proteoglycans (HSPG) on DCs via its heparin-binding domain (HBD), activating PKC-δ and JNK, upregulating DR5, and recruiting FADD to form a death-inducing signaling complex (DISC). HBD.Fc fusion protein alone recapitulates this effect, demonstrating that HSPG cross-linking is sufficient to trigger the apoptotic cascade. Apoptosis assay, Western blotting (PKC-δ, JNK, DR5, FADD), DISC immunoprecipitation, HBD.Fc domain dissection experiment Blood High 18006694
2003 TR6/DcR3 inhibits T cell chemotaxis toward CXCL12/SDF-1α in vitro and in vivo. Solid-phase TR6-Fc or anti-LIGHT mAb similarly inhibit chemotaxis, implicating LIGHT reverse signaling. Mechanistically, TR6 pretreatment prevents Cdc42 activation, p38 MAPK phosphorylation, actin polymerization, and pseudopodium formation in T cells. Transwell chemotaxis assay, Cdc42 activation assay, p38 MAPK phosphorylation assay, actin polymerization assay, in vivo mouse chemotaxis model Journal of immunology High 14500635
2003 TR6 secreted by PBMC inhibits actin polymerization and pseudopodium formation in T cells upon mitogen stimulation, suppressing T cell aggregation induced by alloantigens, anti-CD3, or PHA in a soluble or solid-phase manner. Actin polymerization assay, T cell aggregation assay (PBMC stimulation with alloantigens/anti-CD3/PHA), TR6-Fc solid-phase treatment Journal of cellular biochemistry Medium 12761893
2009 DcR3 protects beta islet cells from apoptosis induced by FasL, LIGHT, and TL1A. DNA microarray analysis of DcR3 transgenic islets revealed that Adcyap1 is upregulated >700-fold and Bank1 is downregulated 50-fold after cytokine assault. Forced overexpression of Adcyap1 or knockdown of Bank1 in insulinoma NIT-1 cells each independently protected against cytokine-triggered apoptosis, identifying novel downstream mediators. DNA microarray, transgenic mouse model, siRNA knockdown, plasmid overexpression, apoptosis assay Journal of immunology Medium 20007581
2009 DcR3-Fc protects THP-1 macrophages from apoptosis by upregulating integrin α4 (VLA-4), promoting macrophage aggregate formation. Anti-VLA4 antibody blocks both the anti-apoptotic effect and aggregate formation induced by DcR3-Fc, demonstrating that increased α4 integrin expression is the mechanism of DcR3-mediated macrophage survival. Apoptosis assay (CHX-induced), integrin expression by Western blot/flow cytometry, anti-VLA4 antibody blocking experiment, aggregate formation assay Biochemical and biophysical research communications Medium 19748482
2011 DcR3 binds to TL1A expressed on rheumatoid synovial fibroblasts (RA-FLS) and negatively regulates cytokine-induced cell proliferation. This DcR3-TL1A signaling represents a 'reverse signaling' mode where DcR3 acts as a ligand rather than a decoy receptor. Cell proliferation assay, binding assay in RA-FLS, cytokine stimulation experiments International journal of molecular medicine Low 21537832
2009 DcR3 suppresses Th17 immune responses; DcR3.Fc treatment of PLP-specific lymph node cells suppresses IFN-γ and IL-17 production and reduces proportion of Th17 cells. DcR3.Fc treatment of CD4+ T cells with defective FasL did not suppress IL-17, demonstrating that DcR3-mediated IL-17 suppression depends on disruption of Fas-FasL interactions. Lymph node cell culture, cytokine ELISA, flow cytometry (Th17 proportion), FasL-defective T cell experiment Journal of neuroimmunology Medium 19269042
2010 DcR3 inhibits p53-dependent apoptosis in lung cancer cells. Knockdown of DcR3 in p53-expressing cells sensitizes them to γ-irradiation by inducing p53-dependent Fas-mediated apoptosis pathway. In p53-deficient H1299 cells, DcR3 knockdown had no effect on survival after irradiation, but introduction of p53 restored sensitivity. Overexpression of DcR3 increased survival of radiosensitive cells. siRNA knockdown, clonogenic survival assay, p53 re-introduction experiment, Western blot International journal of radiation biology Medium 20597837
2015 DcR3 attenuates influenza A virus-induced macrophage activation by inactivating PKC-α and activating STK10 (a negative regulator of cell migration), thereby suppressing ERK and JNK activation. Proteome-wide phosphoproteomic mapping identified these kinase targets. DcR3-transgenic mice show reduced pulmonary infiltration and cytokine levels, and recombinant HBD.Fc (heparin-binding domain of DcR3) recapitulates protection, indicating HSPG-dependent signaling. Phosphoproteomic mapping, Western blot (ERK, JNK, PKC-α, STK10), DcR3 transgenic mouse, HBD.Fc domain experiment Journal of molecular medicine Medium 25940317
2017 DcR3 mediates neuroprotection in an Alzheimer's disease model by interacting with heparan sulfate proteoglycans (HSPGs) and activating IL-4+YM1+ M2a-like microglia, reducing Aβ-induced proinflammatory cytokines and promoting phagocytosis. Co-immunoprecipitation confirmed DcR3-HSPG interaction in brain tissue of APP/DcR3 transgenic mice. APP/DcR3 transgenic mouse cross, immunostaining, ELISA, qPCR, immunoprecipitation (DcR3-HSPG), in vitro macrophage polarization assay Molecular neurodegeneration Medium 28438208
2012 DcR3 binds to epithelial ovarian cancer cells via heparan sulfate proteoglycans (HSPGs); binding is inhibited by heparin and heparinase treatment. DcR3 binding via HSPGs (Syndecan-2 and CD44v3) alters platinum chemotherapy responsiveness and modulates BRCA1 expression (increase in SKOV-3/OVCAR-3, decrease in CaOV3), affecting DNA repair pathways. Heparin/heparinase competition binding assay, RT-PCR array, Western blot (BRCA1), MTT cell viability assay BMC cancer Medium 22583667
2013 Missense mutations in DcR3 (T56I and H122Y) identified in SLE patients exhibit altered binding kinetics to FasL and significantly increase lymphocyte proliferation compared to wild-type DcR3 protein, demonstrating gain-of-function mutations that perturb receptor-ligand interaction. DNA sequencing, recombinant mutant protein production, FasL binding kinetics assay, lymphocyte proliferation assay The Journal of rheumatology Medium 23729807
2018 DcR3 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of gastric cancer cells via the PI3K/AKT/GSK-3β/β-catenin signaling pathway. DcR3 knockdown reduces p-AKT, p-GSK-3β, and β-catenin levels; DcR3 enhances N-cadherin and Vimentin expression while decreasing E-cadherin. shRNA stable knockdown, proliferation/invasion/migration assays, Western blot (PI3K/AKT pathway components, EMT markers) OncoTargets and therapy Medium 30050309
2016 DcR3 is essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) in colorectal cancer cells. DcR3 overexpression enhances CRC proliferation and migration in vitro and tumorigenesis in vivo; DcR3 knockdown attenuates CRC tumorigenesis and metastasis in vivo. DcR3 expression correlates with TGF-β3/SMAD-EMT signaling components. shRNA knockdown, DcR3 overexpression, in vitro proliferation/migration assays, in vivo xenograft model, Western blot (SMAD pathway, EMT markers) Oncotarget Medium 27764793
2019 DcR3 promotes pancreatic cancer proliferation and invasion through a positive feedback loop: DcR3 activates STAT1 phosphorylation, leading to increased IRF1, which then increases DcR3 transcriptional activity. DcR3 also promotes CEACAM1 expression through activated IRF1. Loss-of-function and gain-of-function experiments, Western blot (STAT1 phosphorylation, IRF1), transcriptional reporter assay, in vitro proliferation/invasion assays, in vivo tumor growth assay American journal of cancer research Medium 31911850
2019 DcR3 overexpression in hepatocellular carcinoma is mediated by the TGFβ3-Smad-Sp1 signaling pathway, which directly targets DcR3 promoter regions. DcR3 overexpression promotes Th2 and Treg cell differentiation while inhibiting Th1 cell differentiation; DcR3 knockdown restores CD4+ T cell immunity. Promoter analysis, ChIP/reporter assay (TGFβ3-Smad-Sp1 targeting DcR3 promoter), T cell differentiation assays, DcR3 knockdown and overexpression Oncogenesis Medium 31409774
2017 DcR3 promotes hepatoma cell migration by downregulating E-cadherin expression and activating NF-κB signaling (IκBα degradation and p65 nuclear translocation). DcR3 expression inversely correlates with E-cadherin expression in liver cancer tissues. Immunofluorescence, flow cytometry, Western blot (E-cadherin, IκBα, p65), immunohistochemistry of clinical samples Oncology reports Low 28560426
2018 Up-regulation of DcR3 by microbial toxins (LPS, LTA, zymosan) in HUVECs proceeds through the NF-κB signaling pathway; NF-κB inhibitor PDTC decreased DcR3 expression, while JNK (SP600125) and p38 MAPK (SB203580) inhibitors had no effect on DcR3 mRNA or protein levels. RT-PCR, ELISA, pharmacological pathway inhibition (PDTC, SP600125, SB203580) BMC biochemistry Medium 30587127
2024 ZNF37A binds to the TNFRSF6B/DcR3 promoter region and suppresses its transcriptional activity. Reduced ZNF37A expression induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer cells; TNFRSF6B knockdown restores sensitivity to chemoradiotherapy. Promoter binding assay, transcriptional activity assay, shRNA knockdown, genome-wide expression profiling, functional apoptosis/survival assays Translational oncology Medium 39571490
2011 DcR3 induces chondrocyte proliferation in osteoarthritis chondrocytes via ERK (MAPK) signaling specifically. DcR3-Fc-induced proliferation is blocked by MEK1/2 inhibitor PD098059 and by anti-FasL blocking antibody, but not by anti-LIGHT or anti-TL1A antibodies, establishing that the proliferative effect is mediated through DcR3 binding to FasL and ERK activation. WST proliferation assay, Western blot (ERK, p38, JNK phosphorylation), MEK inhibitor, ligand-blocking antibodies, TUNEL/caspase Western blot (apoptosis) Osteoarthritis and cartilage Medium 21420502

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 526 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.) 96 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
2011 Decoy strategies: the structure of TL1A:DcR3 complex. Structure (London, England : 1993) 56 21300286
2003 Death decoy receptor TR6/DcR3 inhibits T cell chemotaxis in vitro and in vivo. Journal of immunology (Baltimore, Md. : 1950) 56 14500635
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
2016 Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure (London, England : 1993) 38 27806260
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
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) 32 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 Evidence of epistasis between TNFRSF14 and TNFRSF6B polymorphisms in patients with rheumatoid arthritis. Arthritis and rheumatism 18 20187130
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
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
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 14 23449012
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 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
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 12 30537218
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
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
2017 Identification and preclinical evaluation of the small molecule, NSC745887, for treating glioblastomas via suppressing DcR3-associated signaling pathways. Oncotarget 6 29552282
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
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
2024 ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients. Translational oncology 4 39571490
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
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

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