Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.
Gene References into Functions
CD137L-dendritic cells (CD137L-DCs) express high levels of adhesion molecules, display strong attachment.PMID:27431276
TNFSF9 exerts an inhibitory effect on hepatocellular carcinoma and may be a tumor suppressor.PMID:28547807
4-1BB and 4-1BBL qualify as markers for prediction of patients' course and represent a valuable screening target for patients with acute myeloid leukemia at initial diagnosis.PMID:27388616
the results from this study show that the costimulatory 4-1BB ligand fortifies an antigen-rich melanoma cell line with enhanced antigen-specific stimulation of CD8 T cellsPMID:27564312
the role of CD137-CRDI (cysteine rich domain I) in the binding of CD137-CD137L was further investigated.PMID:27430526
blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.PMID:26872462
CD137L is overexpressed in non-small cell lung cancer specimens and positive expression of CD137L was associated with better overall survival.PMID:25631633
In vitro immunotherapy is described for anti-prostate cancer effects of cytotoxic T lymphocytes induction by recombinant adenovirus mediated PSMA/4-1BBL dendritic cells.PMID:26125931
vaccination with recombinant attenuated Salmonella harboring the CEACAM6 and 4-1BBL gene efficiently increased the number of CD3+CD8+ TIL and NK cells, decreased the number of FOXP3 cells and inhibited the development of DMH-induced colorectal cancerPMID:25872647
Elevated plasma levels and monocyte-associated expression of CD137 ligand in patients with acute atherothrombotic strokePMID:24899613
Hence, the targeted combination of IL-15 and 4-BBL in the form of a trifunctional antibody-fusion protein is a promising new approach for cancer immunotherapy.PMID:24198185
monocytes interact with iNKT cells to increase expression of 4-1BBL and 4-1BB, and in conjunction with this pathway, maintain their numbers at baseline.PMID:24639347
TIRAP and IRAK2 are critical for the sustained inflammatory response that is mediated by late-phase signaling by the TLR-4-1BBL complex.PMID:24084649
this is the first study to indicate that this member of the TNF superfamily, CD137, is modulated by SAHA treatment in breastPMID:22797667
Data show that TNFR1 associates with CD137L and is required for CD137L reverse signaling.PMID:23620528
CD137L is a novel diagnostic marker of subtypes of non-Hodgkin B-cell lymphomas.PMID:23095505
signaling through CD137L in non-hematopoietic cells such as epithelial cells and endothelial cells has been shown to play an essential role in sterile inflammation by regulating immune cell recruitment. [Review]PMID:22526397
Stimulation of non-adherent PBMC with OVCAR-3 cells expressing 4-1BB ligand (4-1BBL) or IL-12 resulted in preferential expansion of the NK cell population.PMID:22021067
Data indicate that ex4-1BBL augments 4-1BB expression not only on the primed T cell, but also on DC.PMID:21745658
The expression of CD137L might play an important role in the development of laryngeal carcinomas.PMID:20422976
4-1BBL and TRAF1 in the CD8 T cell response to influenza virus and HIVPMID:21153322
K562-MICA-4-1BBL-IL-15 cells would be developed for expansion of NK cells ex vivo and may have important implications for clinical immunotherapy.PMID:20670353
These data point to a hitherto unrecognized role of CD137 and CD137 ligand in multiple myeloma cell biology.PMID:20520765
TNFSF9 mRNA levels in peripheral blood mononuclear cells may be associated with primary biliary cirrhosis progression.PMID:20303781
Cocultures of Natural killer (NK) cells with CD137L transfectants confirmed that human CD137 inhibits NK-cell reactivity, while activating signals were transduced by its counterpart on NK cells in mice.PMID:20008791
the structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamilyPMID:20032458
4-1BBL and 4-1BB may have immunomodulatory functions, as shown by the anti-leukemia activity of MS-275 histone deacetylase inhibitorPMID:19759901
4-1BBL provides a costimulatory signal for T cell activation, thereby allowing T cell expansion as well as cytokine production and the development of cytolytic effector function.PMID:11994439
Stimulation of 4-1BBL on DCs with 4-1BB-Fc or with 4-1BB-transfected Jurkat cells resulted in acquisition of capacity for the immature DCs to produce IL-12, suggesting that 4-1BBL may be an important mediator for maturation of CD11c(+) myeloid DCsPMID:12590704
4-1 BB ligand can costimulate human CD28- T cells, resulting in cell division, inflammatory cytokine production, increased perforin levels, enhancement of cytolytic effector function, as well as the up-regulation of the anti-apoptotic protein Bcl-X(L).PMID:12645943
First evidence of expression and synthesis of CD137 and its ligand by human brain cells.PMID:13130507
Data show that reverse signaling via 4-1BB-ligand enhanced interleukin-12beta mRNA and the secretion of IL-12 p70 in various antigen-presenting cells, including monocytes.PMID:14746806
4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis.PMID:14752253
Data suggest that levels of soluble 4-1BB and 4-1BB ligand in sera at the time of diagnosis may be indicative of the severity and outcome of rheumatoid arthritis.PMID:15031666
trimeric CD137L (4-1BBL) requires cross-linking for its T cell co-stimulation activityPMID:16204238
Signaling through 4-1BB-L allows B cells to proliferate and the expression of its ligand, by the intra-tumoral mesh of follicular dendritic cells (FDC), could thus serve as a paracrine loop facilitating growth and survival of MCL cellsPMID:16287062
Significantly lower CD137 ligand is associated with colorectal cancer patientsPMID:16596186
Elevated plasma levels of 4-1BBL in multiple sclerosis patients may function as a self-regulatory mechanism of the 4-1BB/4-1BBL pathway involved in the disease process.PMID:16970683
Here we document a function for the TNF family member 4-1BB ligand (4-1BBL) in sustaining TLR-induced TNF productionPMID:17496895
Reverse signalling by CD137 ligand is mediated by protein tyrosine kinases, p38 mitogen activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1,2, MAP/ERK kinase (MEK), Phosphoinositide-3-kinase (PI3-K) and protein kinase A (PKA).PMID:17855813
selective immunosuppression through MSCs may perhaps occur partly through an increase in CD137L+ on T-lymphocytesPMID:17972956
T cells that had become non-responsive to anti-CD3 could be reactivated to proliferate when costimulated with 4-1BBL, either alone or combined with CD80/CD86.PMID:17977894
CD80 and 4-1BBL induce auto- and transcostimulation in tumor cellsPMID:18026115
deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune responsePMID:18395851
PGE(2) induced the expression of the costimulatory molecules OX40L, CD70, and 4-1BBL on human dendritic cells.PMID:19029446
in cells costimulated with CD80/86 that had downregulated CD28 expression and ceased to proliferate, reactivation of proliferation by 4-1BBL costimulation also restored their CD28 expressionPMID:19217084
(c)4-1BBL can be expressed on mononuclear blood cells in acute myeloid leukemia, myelodysplasia or non-Hodgkin lymphoma and can be coexpressed on lymphoid or myeloid malignant cells and on dendritic cells differentiated from AML-blasts.PMID:19225975
reverse signaling of 4-1BBL promotes the differentiation of potent T(h)1-inducing dendritic cells from human monocytes.PMID:19684160
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Subcellular Location
Membrane; Single-pass type II membrane protein.
Protein Families
Tumor necrosis factor family
Tissue Specificity
Expressed in brain, placenta, lung, skeletal muscle and kidney.