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Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.
Gene References into Functions
TNFSF15 polymorphisms may contribute to genetic susceptibility of inflammatory bowel disease (Meta-Analysis) PMID: 29873318
TL1A modulated Rheumatoid arthritis-fibroblast-like synoviocytes migration and Indian hedgehog signaling pathway using TNFR2. PMID: 29748156
TL1A can induce tumor cell proliferation and promote the occurrence of colitis-associated colorectal cancer by activating Wnt/beta-catenin pathway. PMID: 29796912
TNFSF15, a cytokine mainly produced by blood endothelial cells, facilitates tumor lymphangiogenesis by upregulating VEGFC expression in A549 cells. PMID: 29890027
Results suggested that TNFSF15 (rs3810936 and rs4979462) SNPs may confer susceptibility to systemic lupus erythematosus (SLE) risk, which were significantly associated with the clinical phenotypes of SLE. PMID: 29803925
Three alternatively spliced isoforms of VEGI, VEGI174, VEGI192 and VEGI251 have been documented. This study investigated the effects of VEGI174 and its functional domains (V7 and V8) on epithelialmesenchymal transition (EMT) in renal cell carcinoma (RCC) cells in vitro. Overexpression of VEGI174, V7 or V8 inhibited EMT. PMID: 28656288
Results provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including Crohn's disease and primary biliary cholangitis. PMID: 27507062
single variant analysis detected a previously unreported psoriasis risk locus at TNFSF15 (rs6478108) PMID: 28973304
play a role in the development of systemic sclerosis PMID: 28397078
the DR3/TL1A pathway directly enhances human OC formation and resorptive activity, controlling expression and activation of CCL3 and MMP-9. PMID: 28062298
the blocking of tumor necrosis factor receptor 2 (TNFR2) decreased TL1A-stimulated IL-6 production by rheumatoid arthritis fibroblast-like synoviocytes. PMID: 27081759
Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene. PMID: 28624054
TL1A differentially induces expression of TH17 effector cytokines IL-17, -9, and -22 and provides a potential target for therapeutic intervention in TH17-driven chronic inflammatory diseases. PMID: 27733581
Our findings indicate that VEGI174 prevents progression and tumor metastasis through inhibiting epithelial-mesenchymal transition (EMT) in renal cell carcinoma (RCC) in vivo. This may provide a new approach for the treatment of RCC PMID: 28739718
Data suggest that human regulatory T-lymphocytes express DR3 and demonstrate DR3/TL1A-mediated activation of signaling via MAP kinases and NFkappaB. (DR3 = death receptor 3; TL1A/TNFSF15 = tumor necrosis factor [ligand] superfamily, member 15) PMID: 28337757
These results raise the possibility for involvement of TL1A/DR3/DR3-mediated mechanisms in epithelial-mesenchymal interactions and the development of inflammation-induced intestinal fibrosis in Crohn's disease. PMID: 27665176
rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to Inflammatory Bowel Disease in Han-Chinese patients. PMID: 28456797
results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella PMID: 28197769
(188)Re-NGR-VEGI has the potential as a theranostic agent. PMID: 26768609
miRNA-31 can directly bind to the 3-UTR of TNFSF15, thereafter negatively regulating its expression in Caco2 cells. PMID: 27188743
There were significant associations of rs3810936, rs6478108, rs6478109, rs7848647 with CD in Korean pediatric patients (P = 6.5x10(-8), P = 1.3x10(-8), P = 3.7x10(-8), P = 2.9x10(-8), respectively). PMID: 25998826
Patients with mild traumatic brain injury (TBI) exhibited higher VEGI levels than those with moderate and severe TBI. PMID: 26945876
Biologics beyond TNF-alpha inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders. PMID: 26810853
Rs3810936 of TNFSF15 were related to the risk of ankylosing spondylitis PMID: 26823868
Higher TL1A levels were associated with early stage chronic lymphocytic leukemia. PMID: 26393680
TL1A-induced cell death is directly mediated through DR3. PMID: 26509650
Plasma levels of TL1A were significantly higher in newly diagnosed SLE patients compared with controls, and were positively associated with SLE disease activity index. PMID: 25929716
This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients PMID: 25778932
Results show that subjects with TNFSF15 -358CC genotype were at higher risks for developing gastric adenocarcinoma in the Helicobacter pylori infected group. PMID: 25251497
The data indicate that TL1A may contribute to pathogenesis of inflammatory bowel diseases via local but not systemic induction of IL-17A but not IL-4, IL-13 or IFN-gamma. PMID: 26072972
study has defined the increased serum and SF samples levels of TL1A and DcR3 in patients with rheumatoid arthritis (RA); findings support the hypothesis that TL1A and DcR3 may contribute to the pathogenesis of RA PMID: 25647275
TNFSF15 SNPs, rs6478108 and rs4574921, may be independent genetic predictive factors for the development of stricture/non-perianal penetrating complications and perianal fistula, respectively. PMID: 24835165
TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells PMID: 25148371
Addition of TL1A to IL-1beta + IL-23 also augmented ILC3 proliferation PMID: 26046454
This study shows an association between TNFSF15-rs3810936 and AAU and suggests that the TL1A/DR3 pathway may be implicated in the pathogenesis of this disease. PMID: 26200500
associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population PMID: 25501099
These results suggested that TL1A could promote Th17 differentiation in rheumatoid arthritis via the activation of RORc, and this effect may be mediated by the binding of TL1A with DR3. PMID: 24832108
TL1A blood levels are elevated in psoriasis patients; TL1A expression is higher in psoriatic lesions than in normal skin PMID: 25908025
Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1. PMID: 25899471
Soluble TL1A synergized with IL-23 to stimulate peripheral blood mononuclear cells from patients with psoriasis vulgaris to produce IL-17. PMID: 25200589
This meta-analysis indicated that most of the seven TNFSF15 polymorphisms (except for rs4263839) were risk factors contributed to CD and UC susceptibility. The differences in ethnicity did not influence the risk obviously. PMID: 25028192
DR3 is expressed in some interstitial vascular endothelial cells (EC) in human kidney in situ; these EC also respond to its ligand TL1A by activating NF-kappaB. PMID: 25399326
Mechanisms mediating TNFSF15:DR3 contributions to pattern recognition receptor outcomes included TACE-induced TNFSF15 cleavage to soluble TNFSF15; soluble TNFSF15 then led to TRADD/FADD/MALT-1- and caspase-8-mediated autocrine IL-1 secretion. PMID: 25197060
This is the first report of the association between early Crohn's disease and the TNFSF15 single nucleotide polymorphisms. PMID: 25664710
Tumor-infiltrating natural killer and CD4(+) T cells under the influence of cancer cells significantly increase the production of IFNgamma, which in turn inhibits TNFSF15 expression in vascular endothelial cells. PMID: 24141405
may play an important role in the pathogenesis of primary biliary cirrhosis PMID: 24016146
Our data demonstrate a key role for TL1A in promoting ILC2s at mucosal barriers. PMID: 24220298
Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in Crohn's disease patients with TNFSF15 but not with a NOD2 genetic background PMID: 24783249
genetic polymorphism is associated with psoriasis and psoriatic arthritis in Hungarians PMID: 24269700
attenuated S. typhimurium carrying the dual function plasmid VEGI151/survivin cannot only be specifically enriched in the tumor tissue, but also showed a synergistic antitumor effect in vivo. PMID: 23404494
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Subcellular Location
Membrane; Single-pass type II membrane protein.; [Tumor necrosis factor ligand superfamily member 15, secreted form]: Secreted.
Protein Families
Tumor necrosis factor family
Tissue Specificity
Specifically expressed in endothelial cells. Detected in monocytes, placenta, lung, liver, kidney, skeletal muscle, pancreas, spleen, prostate, small intestine and colon.