Affinage

TNFSF15

Tumor necrosis factor ligand superfamily member 15 · UniProt O95150

Length
251 aa
Mass
28.1 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFSF15 (TL1A/VEGI) is a TNF-superfamily type II transmembrane cytokine that operates at the interface of immune costimulation and vascular biology, signaling principally through the death-domain receptor DR3 (TNFRSF25) and being antagonized by the decoy receptor TR6/DcR3 (PMID:11911831, PMID:19522538). Engagement of DR3 nucleates a TRADD–TRAF2–RIP signaling complex that activates NF-κB, ERK, JNK and p38 MAPK, with NF-κB-driven c-IAP2 setting the threshold between survival and apoptosis (PMID:12882979). Soluble trimeric TL1A, generated by metalloprotease/TACE-mediated ectodomain shedding, fully activates DR3 without requiring secondary oligomerization and triggers receptor internalization (PMID:26509650, PMID:15847792, PMID:25197060). On immune cells TL1A is a potent T cell costimulator: it increases IL-2 responsiveness and proinflammatory cytokine secretion (PMID:11911831), drives Th17 proliferation and effector function in autoimmune disease (PMID:18411337), expands and modulates Foxp3+ regulatory T cells through DR3 (PMID:20962771, PMID:23319737), and acts upstream of TNFα to elicit cytokine production from effector T cells (PMID:23250276). In macrophages TNFSF15:DR3 amplifies pattern-recognition-receptor signaling, using a FADD/MALT-1/caspase-8 branch for autocrine IL-1 secretion and a distinct TRAF2/RIPK1/RIP3 branch to drive ROS-, NOS2- and autophagy-dependent antimicrobial clearance (PMID:25197060, PMID:32827707). TL1A expression is induced in antigen-presenting cells by FcγR engagement, bacteria and TLR signaling, while alveolar and airway epithelium express it constitutively as an alarmin that cooperates with IL-33 to push ILC2s into an IL-9-high state initiating allergic airway inflammation (PMID:17371957, PMID:19839006, PMID:38597952). In the vasculature TL1A inhibits endothelial cell and endothelial progenitor proliferation, induces caspase-3-dependent apoptosis, and suppresses tumor vascularization and vasculogenesis—the latter by degrading membrane VEGFR1 while upregulating soluble VEGFR1, suppressing VEGF via a JNK–GATA3–miR-29b axis, and assembling a DR3–SHP-1–VEGFR2 complex that dephosphorylates VEGFR2 (PMID:9872942, PMID:9880523, PMID:23918400, PMID:27589684, PMID:28183800). Membrane-bound and soluble TL1A are functionally divergent—membrane TL1A drives adaptive T cell responses whereas soluble TL1A drives innate type 2 inflammation (PMID:29335258)—and direct DR3 signaling on fibroblasts via Rho signaling promotes intestinal and pulmonary fibrosis (PMID:33097818, PMID:24850426, PMID:32958689). Disease-associated TNFSF15 haplotypes alter its expression and PRR-induced signaling, linking the gene to inflammatory bowel disease (PMID:25197060, PMID:30199539, PMID:19262684).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    Establishing that the endothelium-restricted cytokine VEGI/TL1A is an endogenous angiogenesis suppressor answered whether a TNF-family ligand could act on the vasculature itself rather than on immune cells.

    Evidence cDNA cloning from HUVEC, endothelial proliferation assays, and gene transfer in a murine colon cancer model with histological vascularization analysis

    PMID:9872942

    Open questions at the time
    • Receptor not yet identified at this stage
    • Mechanism of growth inhibition undefined
  2. 1999 High

    Demonstrating TL1A-induced endothelial and tumor-cell apoptosis through SAPK/JNK, p38 and caspase-3, not neutralized by soluble TNF receptors or anti-TNF antibodies, established that TL1A acts via a distinct receptor from TNF.

    Evidence Endothelial/myeloid apoptosis assays, kinase assays, dominant-negative c-Jun, pharmacological inhibitors, EMSA and PARP cleavage

    PMID:10597252 PMID:9880523

    Open questions at the time
    • Receptor identity unresolved
    • Relationship between proapoptotic and NF-κB outputs not defined
  3. 2002 High

    Identifying DR3 as the signaling receptor and TR6/DcR3 as the decoy receptor, together with T cell costimulatory activity, unified the vascular and immune activities under a single ligand-receptor system.

    Evidence Ligand-receptor binding, NF-κB reporter and apoptosis assays, and T cell costimulation assays in vitro and in vivo

    PMID:11911831

    Open questions at the time
    • Downstream adaptor complex not yet mapped
    • Cell-type basis for apoptosis vs. costimulation outcome unclear
  4. 2003 High

    Defining the TRADD–TRAF2–RIP complex and the NF-κB/c-IAP2 survival circuit explained how DR3 partitions between proinflammatory signaling and apoptosis.

    Evidence Co-immunoprecipitation of the signaling complex, MAPK inhibitors, c-IAP2 RNAi, and apoptosis assays in TF-1 cells

    PMID:12882979

    Open questions at the time
    • Stoichiometry of the complex not resolved
    • Cell-type determinants of the survival/death balance unaddressed
  5. 2005 Medium

    Characterizing soluble TL1A as a 30–32 kDa secreted product inducible by IL-1 and TNF, and an isoform (VEGI-192) with vascular-selective antitumor activity, established cytokine-regulated production and clinical anti-angiogenic potential.

    Evidence ELISA, Western blot, affinity purification from HUVEC medium; recombinant protein systemic delivery in Lewis lung carcinoma

    PMID:15847792 PMID:16061878

    Open questions at the time
    • Protease responsible for shedding not identified here
    • Mechanism of vascular-cell selectivity unexplained
  6. 2009 High

    The crystal structure of the TL1A ectodomain and definition of the DR3/DcR3 binding interface provided the structural basis for receptor engagement within the TNF superfamily.

    Evidence X-ray crystallography at 2.5 Å with site-directed mutagenesis and binding assays

    PMID:19522538

    Open questions at the time
    • No co-structure with DR3 or DcR3
    • Conformational basis for signaling not addressed
  7. 2009 Medium

    Showing that bacteria and FcγR/TLR signaling induce TL1A in APCs to enhance T cell IFN-γ, and that VEGI blocks endothelial progenitor differentiation via DR3, extended TL1A function into both innate-adaptive crosstalk and progenitor-cell vasculogenesis.

    Evidence Bacterial/TLR stimulation with p38 and NF-κB inhibitors and T cell co-culture; in vitro EPC differentiation with stage-dependent signaling and anti-DR3 neutralization

    PMID:17371957 PMID:19329781 PMID:19839006

    Open questions at the time
    • Stage-specific receptor regulation not mechanistically explained
    • In vivo relevance of EPC effects limited
  8. 2008 High

    Genetic TL1A knockout linking DR3-high Th17 cells to autoimmune disease severity established TL1A as a driver of pathogenic effector T cell responses.

    Evidence TL1A-KO mice in EAE, flow cytometry of Th17 cells, DC co-culture differentiation assays

    PMID:18411337

    Open questions at the time
    • DR3-proximal signaling in Th17 cells not dissected
    • Contribution of other T cell subsets not resolved here
  9. 2010 Medium

    Transgenic and membrane-form studies revealed TL1A both expands/modulates Tregs and signals through cell-cell contact, showing the cytokine tunes regulatory as well as effector arms of immunity.

    Evidence DC-specific TL1A transgenic mice with Treg proliferation/suppression assays; membrane TL1A expression in HEK-293 with DR3-Fc binding and T cell IFN-γ readout

    PMID:20403353 PMID:20962771

    Open questions at the time
    • Molecular basis of Treg suppression attenuation unclear
    • Balance of effector vs. regulatory outcomes context-dependent
  10. 2011 Medium

    Identifying the AMPK–LITAF promoter axis defined a transcriptional control mechanism for TNFSF15 connecting metabolic signaling to its anti-angiogenic output.

    Evidence shRNA and dominant-negative AMPK, LITAF–promoter binding assay, proliferation assays, and xenograft model

    PMID:21217782

    Open questions at the time
    • Physiological triggers of AMPK-driven TNFSF15 induction unclear
    • Generality across cell types not established
  11. 2013 Medium

    Dissecting ectodomain-shedding isoforms, Treg-expanding TL1A-Ig, and direct effects on plasma cells and effector T cells refined how distinct TL1A forms produce divergent immune and senescence outcomes.

    Evidence Shedding fragment characterization and senescence assays in HUVECs/EPCs; TL1A-Ig SEC-MALS and in vivo Treg expansion; plasma cell survival and CIA model; CD4+CD161+ T cell stimulation

    PMID:20675618 PMID:23250276 PMID:23319737 PMID:24140642

    Open questions at the time
    • Protease specificities for each fragment incompletely defined
    • Mechanism distinguishing trimer vs. oligomer outputs not yet established
  12. 2014 High

    Mechanistic studies in macrophages, fibroblasts and endothelium established that DR3 signaling outputs branch into distinct adaptor pathways and direct stromal effects, including a definitive fibroblast-driven fibrosis mechanism.

    Evidence Macrophage signaling with TACE/caspase-8/PI3K inhibitors and genotype stratification; DR3-KO and anti-TL1A in colonic fibrosis with primary myofibroblast stimulation; DR3/TNFSF15 siRNA in endothelial apoptosis

    PMID:24850426 PMID:25161149 PMID:25197060

    Open questions at the time
    • Switch determining FADD/caspase-8 vs. other branches not fully defined
    • Fibroblast DR3-proximal signaling not yet mapped at this stage
  13. 2013 High

    Defining the VEGFR1 axis showed TNFSF15 suppresses vasculogenesis by degrading membrane VEGFR1 and upregulating soluble VEGFR1 through Akt/PKC/Src/Erk and Jmjd6-dependent splicing.

    Evidence Endothelial progenitor culture, ubiquitination and phosphorylation Western blots, pathway inhibitors, Jmjd6 knockdown, and in vivo Matrigel model

    PMID:23918400

    Open questions at the time
    • E3 ligase for membrane VEGFR1 degradation unidentified
    • Coordination of degradation and splicing programs unclear
  14. 2016 Medium

    Identifying the JNK–GATA3–miR-29b cascade and the DR3–SHP-1–VEGFR2 ternary complex established direct molecular routes by which TNFSF15 suppresses VEGF production and VEGFR2 signaling.

    Evidence miR-29b 3'-UTR reporter, DR3/JNK/GATA3 siRNA, JNK inhibitor; Co-IP of VEGFR2–DR3–SHP-1 and permeability assays in vitro and in vivo

    PMID:27589684 PMID:28183800

    Open questions at the time
    • How DR3 recruits SHP-1 mechanistically undefined
    • Interplay between VEGF suppression and VEGFR2 dephosphorylation not integrated
  15. 2018 High

    Genetic separation of membrane-bound versus soluble TL1A established that the two forms drive adaptive (T cell) versus innate (ILC) inflammation respectively, resolving long-standing functional ambiguity.

    Evidence Membrane-restricted (cleavage-site mutant) TL1A transgenic mice crossed to DR3-deficient lines, with lung and intestinal pathology readouts

    PMID:29335258

    Open questions at the time
    • Molecular basis for differential cellular targeting unexplained
    • Regulation of shedding in vivo unclear
  16. 2018 Medium

    Defining IBD-risk haplotype effects on TNFSF15 expression and microbiota-dependent and EMT-driven fibrosis pathways connected genetic risk, microbial signals, and stromal pathology mechanistically.

    Evidence Recall-by-genotype fine-mapping and allele-specific expression; germ-free TL1A-transgenic mice with microbiome reconstitution; TGF-β1/Smad3 EMT analysis; FcγR-stimulated monocyte haplotype assays

    PMID:19262684 PMID:29988118 PMID:30199539 PMID:34257516

    Open questions at the time
    • Causal regulatory variant mechanism incompletely defined
    • Specific microbial inducers not conclusively identified
  17. 2020 High

    Defining direct DR3 signaling on fibroblasts and bronchial epithelium via Rho signaling, and macrophage antimicrobial pathways via TRAF2/RIPK1/RIP3, established TL1A as a direct driver of fibrosis and innate host defense distinct from its T cell roles.

    Evidence Fibroblast-selective DR3 deletion with adoptive T cell transfer and RNA-Seq; DR3-KO and recombinant TL1A airway models; macrophage gentamicin protection assays with TRAF2/RIPK1/RIP3 and caspase-8 inhibitors

    PMID:32827707 PMID:32958689 PMID:33097818

    Open questions at the time
    • Rho effectors downstream of DR3 in fibroblasts not pinpointed
    • Switch between antimicrobial and proapoptotic adaptor branches not defined
  18. 2024 High

    Identifying constitutive epithelial TL1A as an alarmin cooperating with IL-33 to generate an IL-9-high ILC2 state established a tissue-resident innate mechanism for initiating allergic airway inflammation.

    Evidence Proteomics, lung intravital microscopy, adoptive transfer of ILC9 cells, and in vitro IL-33+TL1A ILC2 stimulation in mouse models

    PMID:38597952

    Open questions at the time
    • Receptor/signaling integration of IL-33 and TL1A in ILC2s not resolved
    • Human relevance of the ILC9 state not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the same DR3 engagement is routed to opposing fates—survival versus apoptosis, antimicrobial versus proapoptotic adaptor branches, and adaptive versus innate effector programs—remains the central unresolved mechanistic question.
  • No unified model of context-dependent DR3 output selection
  • Determinants of adaptor branch choice (FADD/caspase-8 vs. TRAF2/RIPK1/RIP3) undefined
  • No co-structure of TL1A–DR3 signaling complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
RIPK1SHP-1TNFRSF1BTNFRSF25TNFRSF6BTRADDTRAF2VEGFR2

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TL1A (TNFSF15) is a ligand for DR3 (death domain-containing receptor) and decoy receptor TR6/DcR3. TL1A binding to DR3 induces NF-κB activation and apoptosis in DR3-expressing cell lines, and TR6-Fc protein antagonizes these signaling events. In T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines. Ligand-receptor binding assays, NF-κB reporter assays, apoptosis assays, T cell costimulation assays in vitro and in vivo Immunity High 11911831
2003 TL1A-DR3 interaction induces formation of a signaling complex containing TRADD, TRAF2, and RIP, and activates NF-κB and ERK, JNK, and p38 MAPK pathways. TL1A-induced NF-κB activation produces c-IAP2, which prevents DR3-mediated apoptosis in TF-1 cells. Inhibition of NF-κB or knockdown of c-IAP2 by RNA interference sensitizes cells to TL1A-induced apoptosis. Co-immunoprecipitation of signaling complex, NF-κB reporter assays, MAPK pathway inhibitors, RNA interference (siRNA knockdown of c-IAP2), apoptosis assays The Journal of biological chemistry High 12882979
1999 TL1A (VEGI/TNFSF15) is expressed predominantly in endothelial cells, encodes a type II transmembrane protein, and the secreted (soluble) form directly inhibits endothelial cell proliferation and suppresses tumor vascularization in vivo. Local gene transfer of soluble VEGI caused complete suppression of murine colon cancer growth associated with marked reduction in vascularization. cDNA cloning from HUVEC library, gene transfer/tumor model (MC-38 murine colon cancer), in vitro endothelial cell proliferation assay, histological analysis of vascularization FASEB journal High 9872942
1999 TL1A (TL1) induces apoptosis in endothelial cells via activation of stress-activated protein kinase (SAPK/JNK) and p38 MAPK pathways and caspase-3. TL1-induced apoptosis was reduced by dominant-interfering c-Jun mutant, p38 inhibitor SB203580, and caspase inhibitor ZVAD-fmk. The effect was not inhibited by soluble TNF receptors 1 or 2, indicating a distinct receptor. Endothelial cell apoptosis assays, kinase activity assays (SAPK, p38), dominant-negative mutant expression, pharmacological inhibitors, caspase substrate assays, immunocytochemistry The Journal of biological chemistry High 9880523
1999 VEGI (TNFSF15) activates NF-κB (inducing IκBα degradation and p65 nuclear translocation) and c-Jun N-terminal kinase in myeloid cells, inhibits proliferation of multiple tumor cell lines, and activates caspase-3 leading to PARP cleavage. Its activity cannot be neutralized by anti-TNF antibodies and it does not compete with TNF binding, indicating it acts through a distinct receptor. EMSA (NF-κB activation), reporter gene assay, IκBα degradation assay, JNK kinase assay, cell proliferation assay, caspase-3/PARP cleavage assay Oncogene High 10597252
2005 VEGI-192, a new isoform of TNFSF15, systemically administered suppresses tumor growth and specifically eliminates tumor endothelial cells but not vascular smooth muscle cells, with no liver or kidney toxicity. VEGI expression in normal tissue is restricted largely to endothelial cells by immunohistochemistry. Recombinant protein production, systemic i.p./i.v./s.c. injection in Lewis lung carcinoma mouse model, histological analysis, immunohistochemistry Clinical cancer research Medium 16061878
2005 Soluble TL1A is naturally secreted from HUVECs as a 30–32 kDa protein, and its production is significantly induced by IL-1α and TNF. IL-1 is a more potent inducer than TNF, and the induction is dose- and time-dependent. ELISA development, Western blot under reducing/non-reducing conditions, affinity purification of soluble TL1A from conditioned medium Journal of immunological methods Medium 15847792
2007 TL1A expression in human monocytes and monocyte-derived dendritic cells is specifically induced by FcγR signaling (immune complexes), correlating with surface and secreted TL1A protein. TLR agonists capable of inducing IL-6 and TNF-α do not induce surface or soluble TL1A. TL1A produced by monocytes enhances T cell IFN-γ responses. Stimulation assays with TLR agonists, IFN-γ, and immune complexes; surface expression by flow cytometry; TL1A ELISA; T cell co-culture assays Journal of immunology Medium 17371957
2008 DR3 expression is selectively elevated in Th17 cells, and TL1A promotes proliferation of effector Th17 cells. TL1A-deficient dendritic cells have reduced capacity to support Th17 differentiation and proliferation. In experimental autoimmune encephalomyelitis (EAE), TL1A-knockout animals show decreased clinical severity and reduced Th17 differentiation and effector function. TL1A-knockout mouse generation, EAE model, flow cytometry analysis of Th17 cells, DC co-culture differentiation assays The Journal of experimental medicine High 18411337
2009 Crystal structure of the human TL1A extracellular domain at 2.5 Å resolution reveals a jelly-roll fold typical of the TNF superfamily. Mutagenesis and biochemical characterization define the binding interface for DcR3 and DR3 receptors, suggesting the mode of TL1A–DcR3 interaction differs from other characterized TNF ligand/receptor complexes. X-ray crystallography (2.5 Å resolution), site-directed mutagenesis, biochemical binding assays Biochemistry High 19522538
2009 VEGI (TNFSF15) inhibits the differentiation of endothelial progenitor cells (EPCs) from bone marrow Sca1+ mononuclear cells, decreasing endothelial cell marker expression and capability for adhesion, migration, and capillary-like structure formation. VEGI induces apoptosis of differentiated EPCs but not early-stage EPCs; in early-stage EPCs it increases phospho-ERK and decreases phospho-Akt, while in differentiated EPCs it activates NF-κB, JNK, and caspase-3. DR3 is present only on differentiated EPCs and mediates VEGI-induced apoptosis, as shown by neutralizing anti-DR3 antibodies or recombinant DR3 extracellular domain. In vitro EPC differentiation assay, flow cytometry (EPC markers), adhesion/migration/Matrigel assays, Western blot (signaling), neutralizing antibodies against DR3 Blood High 19329781
2009 Multiple bacterial species (gram-negative, gram-positive, anaerobes) induce TL1A expression in human APCs (monocytes and monocyte-derived DCs) via TLR signaling, which is inhibited by downstream blockade of p38 MAPK and NF-κB. Bacterially induced TL1A production by APCs potentiates CD4+ T-cell IFN-γ production. Bacterial stimulation assays, TL1A mRNA/protein quantification, p38 and NF-κB pathway inhibitors, T cell co-culture IFN-γ assays European journal of immunology Medium 19839006
2011 TNFSF15 is a downstream transcriptional target of AMPK, mediated through LITAF binding to a specific sequence in the TNFSF15 promoter region. AMPK activation by AICAR upregulates TNFSF15, and this is abrogated by shRNA or dominant-negative AMPK α1. TNFSF15 inhibits growth of prostate cancer cells and bovine aortic endothelial cells in vitro, and intratumoral injection of TNFSF15 reduces tumor size and blood vessel number in vivo. shRNA knockdown, dominant-negative AMPK mutant, promoter binding assay (LITAF-TNFSF15 promoter), cell proliferation assay, xenograft tumor model, histological analysis Oncogene Medium 21217782
2010 Sustained TL1A expression on DCs drives goblet cell hyperplasia in the ileum associated with elevated IL-13 levels and increased IL-13- and IL-17-producing T cells. TL1A directly stimulates Treg cell proliferation in vitro and enhances Treg turnover in vivo via DR3 signaling. TL1A also attenuates the ability of Treg cells to suppress conventional T cells, requiring DR3 signaling in either conventional or Treg cells. TL1A transgenic mice (DC-specific expression), IL-13 quantification, flow cytometry of T cell subsets, in vitro Treg proliferation assay, suppression assays Mucosal immunology Medium 20962771
2010 Two functionally distinct isoforms of TL1A are generated by differential ectodomain shedding: TL1A(L72-L251) and a novel shorter fragment TL1A(V84-L251). TL1A overexpression induces premature senescence in HUVECs and endothelial progenitor cells, and knockdown of TL1A partially reverts senescence. The novel TL1A(V84-L251) fragment induces growth arrest and apoptosis in HUVECs. Ectodomain shedding characterization, TL1A overexpression and knockdown (siRNA) in HUVECs and EPCs, senescence assays, apoptosis/growth arrest assays The journals of gerontology. Series A, Biological sciences and medical sciences Medium 20675618
2013 Soluble TL1A-Ig (a dimer of TL1A trimers) signals through TNFRSF25 to rapidly expand Foxp3+ Tregs in vivo (up to 30–35% of CD4+ T cells within 5 days), dependent on TCR engagement with MHC class II. TL1A-Ig-expanded Tregs express high levels of KLRG1 and CD103, are highly suppressive ex vivo, and protect against allergic lung inflammation in a mouse asthma model. TL1A-Ig fusion protein generation/characterization (SEC-MALS), in vivo Treg expansion assay, flow cytometry, MHC class II dependency experiments, asthma model (eosinophil/BAL analysis) Journal of immunology Medium 23319737
2013 TNFSF15 (VEGI) inhibits EPC-supported vasculogenesis by simultaneously promoting mFlt1 (membrane VEGFR1) degradation through Akt deactivation-dependent, ubiquitin-assisted degradation, and upregulating sFlt1 (soluble VEGFR1) expression via the PKC/Src/Erk1/2 signaling pathway. TNFSF15 also promotes alternative splicing of Flt1 in favor of sFlt1 by downregulating nuclear protein Jmjd6, thereby disrupting VEGF/PlGF-induced eNOS and MAPK p38 activation and inhibiting EPC-supported vasculogenesis in vivo. In vitro EPC culture, Western blot (phosphorylation, ubiquitination), pathway inhibitors (PKC, Src, Erk1/2), Jmjd6 knockdown, in vivo Matrigel implant model, alternative splicing analysis Proceedings of the National Academy of Sciences of the United States of America High 23918400
2014 TNFSF15:DR3 interactions in human macrophages amplify PRR-initiated MAPK/NF-κB/PI3K signaling and cytokine secretion. Mechanism involves TACE-induced cleavage of TNFSF15 to soluble form, which then signals via TRADD/FADD/MALT-1 and caspase-8 to induce autocrine IL-1 secretion. The rs6478108 A disease-risk allele is associated with increased TNFSF15 expression and increased PRR-induced signaling and cytokines in macrophages. Human macrophage stimulation assays, pathway inhibitors (TACE, NF-κB, PI3K, MAPK), caspase-8 inhibition, ELISA, genotype-stratified analysis Proceedings of the National Academy of Sciences of the United States of America High 25197060
2014 TL1A directly signals through DR3 on intestinal myofibroblasts to increase collagen and IL-31Ra expression. Blocking TL1A with neutralizing antibody or deletion of DR3 reduces the number of fibroblasts and myofibroblasts and reverses established murine colonic fibrosis, reducing connective tissue growth factor, TGF-β1, and IGF-1 expression. Neutralizing anti-Tl1a antibody treatment in murine colitis model, Dr3 knockout mice, primary intestinal myofibroblast culture with TL1A stimulation, collagen and cytokine quantification Mucosal immunology High 24850426
2015 Soluble trimeric TL1A fully activates DR3-associated pro- and anti-apoptotic signaling pathways without requiring secondary oligomerization. DR3 is efficiently activated by soluble TL1A trimers (similar to TNFR1, unlike TRAIL receptors which require oligomerization). TL1A binding induces DR3 internalization, and the affinity of TL1A-DR3 interaction was measured in a cell-based system. Cell-based DR3 activation assays (apoptosis, NF-κB), comparison with oligomerized vs. non-oligomerized soluble ligand, receptor internalization assay, affinity measurement The FEBS journal Medium 26509650
2016 TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression through activation of the JNK–GATA3 signaling pathway. miR-29b targets the 3'-UTR of VEGF transcript. Blocking TNFSF15 activity (via DR3 siRNA or neutralizing antibody 4-3H) inhibits miR-29b and reinstates VEGF production. JNK inhibitor (SP600125) or JNK siRNA eradicates TNFSF15-induced GATA3 expression; GATA3 siRNA suppresses TNFSF15-induced miR-29b. miRNA expression assay, 3'-UTR reporter assay, siRNA knockdown (DR3, JNK, GATA3), neutralizing antibody, JNK inhibitor (SP600125), qRT-PCR, Western blot Oncotarget Medium 27589684
2017 TNFSF15 inhibits VEGF-induced vascular hyperpermeability in vitro and in vivo through DR3-mediated dephosphorylation of VEGFR2. Upon TNFSF15-DR3 interaction, SHP-1 (a phosphatase) becomes associated with DR3, and a ternary protein complex consisting of VEGFR2, DR3, and SHP-1 is formed, providing the structural basis for VEGFR2 dephosphorylation. In vitro vascular permeability assay, in vivo permeability model, Co-immunoprecipitation (VEGFR2–DR3–SHP-1 complex), Western blot (VEGFR2 phosphorylation), siRNA knockdown FASEB journal High 28183800
2018 Membrane-bound TL1A and soluble TL1A have differential roles: membrane TL1A promotes inflammatory cytokine expression in the lung dependent on DR3 on T cells (adaptive immunity), while soluble TL1A alone is sufficient to induce intestinal type 2 inflammation independently of T cells (innate lymphoid cells). These differential activities were demonstrated using membrane-restricted TL1A-transgenic mice. Generation of membrane-restricted TL1A-transgenic mice (cleavage site mutant), comparison with soluble TL1A-expressing mice, DR3-deficient crosses, lung cytokine and intestinal pathology analysis Journal of immunology High 29335258
2010 Membrane-bound TL1A (TL1A-M) can bind DR3 through cell-cell contact and signal to induce IFN-γ secretion enhancement from IL-12/IL-18-primed CD4+ T cells. This was blocked by anti-TL1A antibody, demonstrating functional signaling capacity of the membrane-bound form. TL1A-M expression in HEK-293 cells, DR3-Fc binding assay, co-incubation with primed T cells, IFN-γ ELISA, antibody blocking FEBS letters Medium 20403353
2013 TL1A directly induces proinflammatory cytokines including TNF-α from CD3+CD161+ (CD4+CD161+) T cells. Anti-TNF-α failed to block TL1A-induced cytokine production, indicating TL1A effects are independent of and upstream of TNFα. Isolation of CD4+CD161+ T cells, TL1A stimulation, cytokine ELISA, anti-TNFα antibody blocking experiments Mucosal immunology Medium 23250276
2013 Plasma cells (but not B cells) express high levels of DR3 and are direct targets of TL1A. In the presence of TL1A, plasma cells survive better and produce more anti-collagen antibody. TL1A gene knockout mice show ameliorated collagen-induced arthritis with reduced pathogenic anti-collagen Ab titers. TL1A KO mouse generation, CIA model, flow cytometry (DR3 expression on B cells and plasma cells), plasma cell survival and antibody production assays Journal of immunology Medium 24140642
2020 Autocrine/paracrine TNFSF15:DR3 interactions are required for optimal PRR-induced bacterial clearance in human macrophages. TNFSF15 induces bacterial uptake via pyruvate dehydrogenase kinase 1 and promotes intracellular bacterial clearance through reactive oxygen species, nitric oxide synthase 2, and autophagy upregulation. The TNFSF15-initiated TRAF2/RIPK1/RIP3 pathway (but not the FADD/MALT-1/caspase-8 pathway) is required for MAPK and NF-κB activation and antimicrobial pathways. Human monocyte-derived macrophage assays, flow cytometry, ELISA, gentamicin protection assay (bacterial clearance), pathway inhibitors (TRAF2, RIPK1, RIP3, FADD, caspase-8), ROS/NOS2/autophagy assays, genotype-stratified analysis of IBD risk carriers Cellular and molecular gastroenterology and hepatology High 32827707
2020 TL1A directly signals through DR3 on lung fibroblasts and bronchial epithelial cells to induce proliferation and production of fibrotic molecules (collagen, periostin), driving airway remodeling. Neutralization of TL1A or genetic deletion of DR3 restricts peribronchial smooth muscle mass and lung collagen accumulation in allergen- and bleomycin-driven mouse models. Recombinant TL1A administered into naive mouse airways drives remodeling independently of innate lymphoid cells and adaptive immunity. Anti-TL1A antibody neutralization, DR3-KO mice, recombinant TL1A instillation in naive mice, human lung fibroblast and bronchial epithelial cell culture with TL1A stimulation, collagen/periostin quantification Journal of immunology High 32958689
2020 Direct TL1A-DR3 signaling on fibroblasts promotes intestinal fibrosis in vivo. Transfer of TL1A-overexpressing T cells into Rag-/- mice with DR3 deleted specifically on fibroblasts (Rag-/-Dr3ΔCol1a2) showed reduced intestinal fibrosis and attenuated fibroblast activation and migration compared to Rag-/- controls, despite similar inflammation. RNA-Seq of TL1A-stimulated fibroblasts identified Rho signal transduction as a major activated pathway, and inhibition of this pathway modulated TL1A-mediated fibroblast functions. Adoptive T cell transfer into Rag-/-, Rag-/-Dr3-/-, and Rag-/-Dr3ΔCol1a2 mice, collagen deposition quantification, RNA-Seq of TL1A-stimulated fibroblasts, Rho pathway inhibition Scientific reports High 33097818
2014 DR3 mediates TNFSF15-induced endothelial cell apoptosis. siRNA-mediated knockdown of DR3 confers resistance to TNFSF15-induced apoptosis. DR3-depleted cells show increased ERK1/2 MAPK activity and upregulation of anti-apoptotic proteins c-FLIP and Bcl-2. Additionally, TNFα-induced apoptosis is also dependent on TNFSF15 upregulation stimulated by TNFα, as TNFSF15 siRNA or neutralizing antibody inhibits TNFα-induced apoptosis. siRNA knockdown of DR3 and TNFSF15, in vivo Matrigel angiogenesis assay, endothelial cell culture apoptosis assays, Western blot (ERK, c-FLIP, Bcl-2), neutralizing antibody (4-3H) The international journal of biochemistry & cell biology Medium 25161149
2024 TL1A is constitutively expressed as an epithelial alarmin in alveolar epithelium at steady state in mice and humans (including airway basal cells). Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low 'ILC9' phenotype and produce large amounts of IL-9. Large-scale proteomic analysis, lung intravital microscopy, and adoptive transfer experiments revealed that IL-9high distinguishes a multicytokine-producing ILC2 state with increased capacity to initiate IL-5-dependent allergic airway inflammation. Proteomic analyses, lung intravital microscopy, adoptive transfer of ILC9 cells, in vitro ILC2 stimulation (IL-33 + TL1A), flow cytometry, IL-9/IL-5 functional assays in mouse models The Journal of experimental medicine High 38597952
2018 The IBD-risk haplotype at TNFSF15 is associated with decreased expression of TNFSF15 by peripheral blood monocytes (at both RNA and protein levels) under various stimulation conditions, maintained after macrophage differentiation. The regulatory polymorphism controlling TNFSF15 expression was localized to the upstream regulatory region of the gene using recall-by-genotype fine-mapping. Genetically regulated TNFSF15 has functional relevance as shown by a T cell costimulation assay. Recall-by-genotype functional fine-mapping, allele-specific expression measurement, monocyte stimulation assays (RNA and protein), macrophage differentiation, T cell costimulation assay PLoS genetics Medium 30199539
2009 TL1A gene haplotype B increases TL1A expression in response to FcγR stimulation in Jewish CD patients positive for OmpC antibody. CD14+ monocytes from patients homozygous for haplotype B express higher levels of TL1A, and peripheral monocytes show increased membrane TL1A expression. SNP haplotyping, monocyte isolation and FcγR stimulation, ELISA for TL1A protein, flow cytometry for membrane TL1A PloS one Medium 19262684
2018 TL1A-mediated intestinal fibrosis and fibroblast activation are dependent on specific microbial populations. In germ-free Tl1a-transgenic mice, the pro-fibrotic and inflammatory phenotype is abrogated. Reconstitution with SPF (but not healthy human) microbiota restores intestinal collagen deposition and fibroblast activation. Candidate organisms correlating with fibrosis were identified and shown to directly impact fibroblast function in vitro. Germ-free Tl1a-transgenic mice, microbiome reconstitution by gavage (SPF vs. human donor stool), collagen deposition quantification, fibroblast migration/activation assays in vitro Mucosal immunology Medium 29988118
2021 TL1A promotes EMT (epithelial-mesenchymal transition) in intestinal epithelial cells via the TGF-β1/Smad3 pathway, with increased expression of IL-13 and EMT transcription factors ZEB1 and Snail1. TL1A-induced EMT is inhibited by anti-TL1A antibody or BMP-7 in vitro. IBD patient tissue analysis, TL1A transgenic mouse DSS-colitis model, HT-29 cell stimulation with TL1A/anti-TL1A/BMP-7, Western blot and qPCR for EMT markers (E-cadherin, FSP1, α-SMA), pathway analysis (TGF-β1/Smad3) Mediators of inflammation Medium 34257516
2018 TL1A mediates RA fibroblast-like synoviocyte (FLS) migration and activates Indian Hedgehog (IHH) signaling, including upregulation of IHH and its receptors PTCH1 and PTCH2. This effect is mediated through TNFR2, and blocking TL1A with TNFR2 antagonist reduces IHH expression and FLS migration. RA-FLS isolation from patients, TL1A stimulation, TNFR2 antagonist blocking, qRT-PCR and Western blot (IHH, PTCH1/2), FLS migration assay European cytokine network Low 29748156
2008 Chicken TL1A (ChTL1A) binds to TNFR2 and decoy receptor 3 (DcR3) and decreases the viability of CHO-K1 cells transfected with chicken TNFR2 or DcR3. ChTL1A acts as a proinflammatory cytokine in chickens, and anti-ChTL1A antibody prevents LPS-induced increases in plasma nitrite/nitrate and acute phase proteins. CHO-K1 transfection with chicken TNFR2/DcR3, cell viability assay, LPS injection in vivo, acute phase protein measurement, anti-ChTL1A antibody neutralization Journal of immunology Low 18523299

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
2003 Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. Journal of immunology (Baltimore, Md. : 1950) 258 14568967
2008 TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology 215 18598698
2008 TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease. The Journal of experimental medicine 187 18411337
1999 VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 140 9872942
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
2007 The T cell costimulator TL1A is induced by FcgammaR signaling in human monocytes and dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 130 17371957
2012 Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα. Gut 127 22684480
2011 TL1A and DR3, a TNF family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation. Immunological reviews 106 22017439
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
1999 TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells. Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and caspase-3-like protease. The Journal of biological chemistry 98 9880523
2011 Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 95 21636646
2019 TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity. Frontiers in immunology 93 30972074
2014 Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis. Mucosal immunology 92 24850426
2018 Inflammation-independent TL1A-mediated intestinal fibrosis is dependent on the gut microbiome. Mucosal immunology 90 29988118
2011 Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. PloS one 89 21264313
2010 Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia. Mucosal immunology 86 20962771
2021 Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 82 34126262
2007 TNFSF15 is an ethnic-specific IBD gene. Inflammatory bowel diseases 80 17663424
2009 IBD-associated TL1A gene (TNFSF15) haplotypes determine increased expression of TL1A protein. PloS one 78 19262684
2015 VEGI attenuates the inflammatory injury and disruption of blood-brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury. Brain research 76 26080076
2009 Microbial induction of inflammatory bowel disease associated gene TL1A (TNFSF15) in antigen presenting cells. European journal of immunology 76 19839006
2012 TL1A/TNFSF15 directly induces proinflammatory cytokines, including TNFα, from CD3+CD161+ T cells to exacerbate gut inflammation. Mucosal immunology 73 23250276
2005 Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. Cytokine 71 15760679
2011 Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria. Nucleic acids research 66 21724600
2011 LITAF and TNFSF15, two downstream targets of AMPK, exert inhibitory effects on tumor growth. Oncogene 65 21217782
2008 TL1A both promotes and protects from renal inflammation and injury. Journal of the American Society of Nephrology : JASN 65 18287561
2015 The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator. Journal of leukocyte biology 63 26188076
2009 TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort. The American journal of gastroenterology 62 19174806
2022 Role of TL1A in Inflammatory Autoimmune Diseases: A Comprehensive Review. Frontiers in immunology 61 35911746
2014 A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8-induced IL-1. Proceedings of the National Academy of Sciences of the United States of America 61 25197060
1999 VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth. Oncogene 61 10597252
2005 VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth. Clinical cancer research : an official journal of the American Association for Cancer Research 60 16061878
2014 The TNFSF15 gene single nucleotide polymorphism rs7848647 is associated with surgical diverticulitis. Annals of surgery 59 24814505
2013 The role of TL1A and DR3 in autoimmune and inflammatory diseases. Mediators of inflammation 59 24453414
2009 Inhibition of endothelial progenitor cell differentiation by VEGI. Blood 56 19329781
2020 The Role of the TL1A/DR3 Axis in the Activation of Group 2 Innate Lymphoid Cells in Subjects with Eosinophilic Asthma. American journal of respiratory and critical care medicine 55 32584596
2014 TNFSF15 is an independent predictor for the development of Crohn's disease-related complications in Koreans. Journal of Crohn's & colitis 52 24835165
2020 Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney international 48 32554042
2013 TNFSF15 inhibits vasculogenesis by regulating relative levels of membrane-bound and soluble isoforms of VEGF receptor 1. Proceedings of the National Academy of Sciences of the United States of America 47 23918400
2012 TNFSF15 Modulates Neovascularization and Inflammation. Cancer microenvironment : official journal of the International Cancer Microenvironment Society 47 22833050
1981 Antitermination and termination functions of the cloned nutL, N, and tL1 modules of coliphage lambda. Gene 46 6211393
2018 An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease. mAbs 45 29436901
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
2011 Down-modulation of TNFSF15 in ovarian cancer by VEGF and MCP-1 is a pre-requisite for tumor neovascularization. Angiogenesis 45 22210436
2017 Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling. Human molecular genetics 44 28973304
2009 VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondria-mediated cancer cell apoptosis. Cell research 44 19918267
2013 Cloning, expression, and functional characterization of TL1A-Ig. Journal of immunology (Baltimore, Md. : 1950) 42 23319737
2013 SUSTAINED TL1A (TNFSF15) EXPRESSION ON BOTH LYMPHOID AND MYELOID CELLS LEADS TO MILD SPONTANEOUS INTESTINAL INFLAMMATION AND FIBROSIS. European journal of microbiology & immunology 40 23638306
2015 The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases. Seminars in arthritis and rheumatism 39 25887448
2020 TL1A inhibits atherosclerosis in apoE-deficient mice by regulating the phenotype of vascular smooth muscle cells. The Journal of biological chemistry 37 32963108
2025 Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD. Gut 36 39266053
2021 Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related Intestinal Fibrosis. Mediators of inflammation 36 34257516
2020 TL1A Promotes Lung Tissue Fibrosis and Airway Remodeling. Journal of immunology (Baltimore, Md. : 1950) 35 32958689
2018 Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease. PLoS genetics 35 30199539
2013 Immunobiology of TNFSF15 and TNFRSF25. Immunologic research 35 24242819
2010 Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors. Angiogenesis 34 21188501
2020 Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo. Scientific reports 33 33097818
2009 Biochemical and structural characterization of the human TL1A ectodomain. Biochemistry 33 19522538
2019 Effects and Mechanism of Constitutive TL1A Expression on Intestinal Mucosal Barrier in DSS-Induced Colitis. Digestive diseases and sciences 31 30949903
2010 Expression of vascular endothelial growth inhibitor (VEGI) in human urothelial cancer of the bladder and its effects on the adhesion and migration of bladder cancer cells in vitro. Anticancer research 31 20150621
2005 Identification of naturally secreted soluble form of TL1A, a TNF-like cytokine. Journal of immunological methods 31 15847792
2024 TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation. The Journal of experimental medicine 30 38597952
2014 TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition. European journal of immunology 29 25404161
2016 TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals. Oncotarget 28 27589684
2015 Soluble TL1A is sufficient for activation of death receptor 3. The FEBS journal 28 26509650
2013 TNF-like ligand 1A (TL1A) gene knockout leads to ameliorated collagen-induced arthritis in mice: implication of TL1A in humoral immune responses. Journal of immunology (Baltimore, Md. : 1950) 28 24140642
2008 Role of chicken TL1A on inflammatory responses and partial characterization of its receptor. Journal of immunology (Baltimore, Md. : 1950) 26 18523299
2024 TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis. Med (New York, N.Y.) 24 38574740
2014 TL1A increased the differentiation of peripheral Th17 in rheumatoid arthritis. Cytokine 23 24832108
2014 Detection rates and phenotypic spectrum of m.3243A>G in the MT-TL1 gene: a molecular diagnostic laboratory perspective. Mitochondrion 23 24846800
2010 Two functionally distinct isoforms of TL1A (TNFSF15) generated by differential ectodomain shedding. The journals of gerontology. Series A, Biological sciences and medical sciences 23 20675618
2020 TNFSF15 Promotes Antimicrobial Pathways in Human Macrophages and These Are Modulated by TNFSF15 Disease-Risk Variants. Cellular and molecular gastroenterology and hepatology 22 32827707
2014 Death receptor 3 mediates TNFSF15- and TNFα-induced endothelial cell apoptosis. The international journal of biochemistry & cell biology 22 25161149
2009 Therapeutic Potential of VEGI/TL1A in Autoimmunity and Cancer. Advances in experimental medicine and biology 22 19760077
2017 Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction. Frontiers in immunology 21 28261213
2022 The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling. Allergy, asthma & immunology research 20 35255540
2022 TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial-Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma. Frontiers in immunology 20 35359966
2006 Vascular endothelial growth inhibitor (VEGI), an endogenous negative regulator of angiogenesis. Seminars in ophthalmology 20 16517446
2016 TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes. International journal of molecular sciences 19 27120595
2017 TNFSF15 inhibits VEGF-stimulated vascular hyperpermeability by inducing VEGFR2 dephosphorylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 28183800
2015 Association of Genetic Variations in TNFSF15 With Acute Anterior Uveitis in Chinese Han. Investigative ophthalmology & visual science 18 26200500
2014 Combining TNFSF15 and ASCA IgA can be used as a predictor for the stenosis/perforating phenotype of Crohn's disease. Journal of gastroenterology and hepatology 18 24783249
2013 Interferon-γ produced by tumor-infiltrating NK cells and CD4+ T cells downregulates TNFSF15 expression in vascular endothelial cells. Angiogenesis 18 24141405
2020 Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF. Arthritis research & therapy 17 32381123
2019 TL1A modulates the severity of colitis by promoting Th9 differentiation and IL-9 secretion. Life sciences 17 31176785
2012 Advancement in the research on vascular endothelial growth inhibitor (VEGI). Targeted oncology 17 22388993
2010 Functional signaling of membrane-bound TL1A induces IFN-gamma expression. FEBS letters 17 20403353
2021 Targeting TL1A/DR3 Signaling Offers a Therapeutic Advantage to Neutralizing IL13/IL4Rα in Muco-Secretory Fibrotic Disorders. Frontiers in immunology 16 34305924
2016 Downregulation of VEGF and upregulation of TL1A expression induce HUVEC apoptosis in response to high glucose stimuli. Molecular medicine reports 16 26936681
2018 Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive Immune Cells. Journal of immunology (Baltimore, Md. : 1950) 15 29335258
2018 TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis. European cytokine network 15 29748156
2014 TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes. PloS one 15 24416448
2023 TL1A promotes the postoperative cognitive dysfunction in mice through NLRP3-mediated A1 differentiation of astrocytes. CNS neuroscience & therapeutics 14 37269079
2021 Analysis of therapeutic potential of preclinical models based on DR3/TL1A pathway modulation (Review). Experimental and therapeutic medicine 14 33986858
2018 Counterbalance: modulation of VEGF/VEGFR activities by TNFSF15. Signal transduction and targeted therapy 14 30101034
2015 Secretion, blood levels and cutaneous expression of TL1A in psoriasis patients. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 14 25908025
2025 TL1A, a novel alarmin in airway, intestinal, and autoimmune disorders. The Journal of allergy and clinical immunology 13 40010414
2018 Role of TNFSF15 in the intestinal inflammatory response. World journal of gastrointestinal pathophysiology 13 30809418
2016 Evaluation of (188)Re-labeled NGR-VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 26768609

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