Details for: TNFSF14

Gene ID: 8740

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TNFSF14

Ensembl ID: ENSG00000125735

Description: TNF superfamily member 14

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 10.79
    rCSI 14.14%
    PRS 83.58
  • hepatocyte CL0000182
    CSI 9.72
    rCSI 17.41%
    PRS 70.73
  • centrilobular region hepatocyte CL0019029
    CSI 5.68
    rCSI 14.83%
    PRS 72.22
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 3.97
    rCSI 7.92%
    PRS 85.68
  • natural T-regulatory cell CL0000903
    CSI 3.82
    rCSI 7.23%
    PRS 93.61
  • CD4-positive helper T cell CL0000492
    CSI 3.17
    rCSI 2.4%
    PRS 84.38
  • alpha-beta T cell CL0000789
    CSI 3.17
    rCSI 3.72%
    PRS 86.1
  • midzonal region hepatocyte CL0019028
    CSI 3.05
    rCSI 7.16%
    PRS 73.62
  • mature T cell CL0002419
    CSI 2.91
    rCSI 2.26%
    PRS 87.2
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.5
    rCSI 1.68%
    PRS 84.37
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.44
    rCSI 2.4%
    PRS 87.99
  • alveolar adventitial fibroblast CL4028006
    CSI 2.25
    rCSI 3.56%
    PRS 73.26
  • group 3 innate lymphoid cell CL0001071
    CSI 2.25
    rCSI 1.69%
    PRS 77.17
  • activated type II NK T cell CL0000931
    CSI 2.14
    rCSI 2.41%
    PRS 86.11
  • bronchus fibroblast of lung CL2000093
    CSI 2.06
    rCSI 1.68%
    PRS 71.35
  • T-helper 17 cell CL0000899
    CSI 2.06
    rCSI 1.64%
    PRS 90.07
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.74
    rCSI 5%
    PRS 89.09
  • periportal region hepatocyte CL0019026
    CSI 1.72
    rCSI 6.68%
    PRS 73.37
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 1.62
    rCSI 2.52%
    PRS 90.71
  • adventitial cell CL0002503
    CSI 1.59
    rCSI 3.8%
    PRS 77.76
  • granulocyte CL0000094
    CSI 1.54
    rCSI 2.35%
    PRS 80.06
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.36
    rCSI 2.32%
    PRS 86.31
  • T-helper 1 cell CL0000545
    CSI 1.3
    rCSI 2.35%
    PRS 89.09
  • intrahepatic cholangiocyte CL0002538
    CSI 1.29
    rCSI 3.11%
    PRS 78.38
  • memory T cell CL0000813
    CSI 1.28
    rCSI 2.46%
    PRS 92.04
  • promonocyte CL0000559
    CSI 1.2
    rCSI 2.06%
    PRS 78.98
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.07
    rCSI 1.29%
    PRS 80.19
  • innate lymphoid cell CL0001065
    CSI 1.06
    rCSI 2.19%
    PRS 70.48
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 1.02
    rCSI 4.64%
    PRS 91.76
  • group 2 innate lymphoid cell CL0001069
    CSI 0.78
    rCSI 4.21%
    PRS 92.5
  • cytotoxic T cell CL0000910
    CSI 0.51
    rCSI 2.95%
    PRS 78.15

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TNFSF14](/details-gene/8740), also known as LIGHT (lymphotoxin-like, exhibits inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes), is a protein-coding gene located on chromosome 19p13.3. As a member of the tumor necrosis factor (TNF) ligand superfamily, [TNFSF14](/details-gene/8740) functions as a cytokine that plays a critical role in the immune system. It acts as a ligand for the herpesvirus entry mediator (HVEM/TNFRSF14) and lymphotoxin beta receptor (LTBR), thereby co-stimulating T cell proliferation and mediating inflammatory responses [Link](https://doi.org/10.1016/s1074-7613(00)80455-0), [Link](https://doi.org/10.4049/jimmunol.164.8.4105). Expression data indicates its high significance in immune cells, particularly [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397)s and various T cell subsets, as well as a notable and unexpectedly high significance in [hepatocyte](/details-cell/CL0000182)s, suggesting a diverse functional role in both systemic immunity and organ-specific immune surveillance. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TNFSF14](/details-gene/8740) highlights its dual role in both the innate and adaptive immune systems, with a prominent and intriguing presence in liver tissue. The highest significance score is observed in [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (CSI: 10.79), a non-classical monocyte subset known for its pro-inflammatory and patrolling functions. This suggests [TNFSF14](/details-gene/8740) may be a key effector molecule expressed by these cells to modulate immune responses in peripheral tissues. Following monocytes, the gene shows strong significance in a variety of T lymphocyte populations, including [CD8-positive, CD28-negative, alpha-beta regulatory T cell](/details-cell/CL0000920), [natural T-regulatory cell](/details-cell/CL0000903), and [CD4-positive helper T cell](/details-cell/CL0000492). This is consistent with its established role in [T cell costimulation](/details-cell/GO:0031295) and proliferation, indicating it is a crucial regulator of T cell activity and homeostasis. A striking feature of the [TNFSF14](/details-gene/8740) expression landscape is its high significance in [hepatocyte](/details-cell/CL0000182)s (CSI: 9.72), specifically within [centrilobular region hepatocyte](/details-cell/CL0019029)s. This high expression in a non-hematopoietic cell type suggests a potential function for [TNFSF14](/details-gene/8740) in liver immunology, such as mediating communication between hepatocytes and liver-resident immune cells or contributing to inflammatory processes during liver injury or infection. The gene is also significant in stromal cells like [alveolar adventitial fibroblast](/details-cell/CL4028006), pointing to a broader role in tissue microenvironments beyond circulating immune cells. ## Pathways and Molecular Function The molecular functions of [TNFSF14](/details-gene/8740) are centered on its activity as a cytokine and its ability to bind TNF family receptors, thereby initiating downstream signaling cascades. Its annotation for [cytokine activity](/details-cell/GO:0005125) and [Tumor necrosis factor receptor binding](/details-cell/GO:0005164) is fundamental to its biological role. These interactions trigger key immune processes such as '[T cell activation](/details-cell/GO:0042110)', '[T cell proliferation](/details-cell/GO:0042098)', and '[T cell chemotaxis](/details-cell/GO:0010818)', which aligns with its high expression in multiple T cell subsets. Mechanistically, [TNFSF14](/details-gene/8740) is implicated in the '[Cytokine signaling in immune system](/details-pathway/R-HSA-1280215)' pathway. It specifically participates in signaling pathways mediated by the TNF receptor superfamily, contributing to both '[positive regulation of canonical nf-kappab signal transduction](/details-cell/GO:0043123)' and '[positive regulation of non-canonical nf-kappab signal transduction](/details-cell/GO:1901224)'. The involvement in these central inflammatory and cell survival pathways underscores its importance in orchestrating immune responses. Furthermore, its role in the '[apoptotic process](/details-cell/GO:0006915)' suggests that, like other TNF family members, it can mediate context-dependent signals for either cell survival and proliferation or programmed cell death. ## Research Directions The expression profile and functional annotation of [TNFSF14](/details-gene/8740) provide a basis for several testable hypotheses regarding its role in health and disease. 1. **Hypothesis 1:** Given its peak expression in pro-inflammatory [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397)s, [TNFSF14](/details-gene/8740) expressed on these cells may be a primary driver of T cell activation and recruitment during the early stages of autoimmune diseases, such as rheumatoid arthritis or inflammatory bowel disease. 2. **Hypothesis 2:** The high expression of [TNFSF14](/details-gene/8740) by [hepatocyte](/details-cell/CL0000182)s is not merely a bystander effect but serves a functional role in liver immune surveillance. Hepatocyte-derived [TNFSF14](/details-gene/8740) may directly co-stimulate liver-resident T cells or NK cells, contributing to the pathogenesis of non-alcoholic steatohepatitis (NASH) or viral hepatitis by promoting a pro-inflammatory microenvironment. **Experimental Approach to Test Hypothesis 2:** To investigate the functional impact of hepatocyte-derived [TNFSF14](/details-gene/8740) on T cell responses, a series of co-culture experiments could be performed. First, [TNFSF14](/details-gene/8740) would be knocked out in a human hepatocyte cell line (e.g., HepG2 or primary human hepatocytes) using CRISPR-Cas9 technology. These knockout hepatocytes and their wild-type counterparts would then be co-cultured with isolated primary human T cells. The effect on T cell function would be assessed by measuring activation markers (e.g., CD25, CD69) via flow cytometry, proliferation using a CFSE dilution assay, and the secretion of key cytokines like IFN-gamma and TNF-alpha into the supernatant via ELISA or multiplex bead array. A significant reduction in T cell activation and proliferation in the presence of knockout hepatocytes would provide direct evidence for the co-stimulatory role of hepatocyte-expressed [TNFSF14](/details-gene/8740). **Therapeutic Potential:** As a cell surface and secreted protein, [TNFSF14](/details-gene/8740) is an accessible therapeutic target. Its dual role in promoting T cell responses presents two opposing therapeutic strategies. In autoimmune diseases or chronic inflammatory conditions characterized by excessive T cell activity, **inhibition** of [TNFSF14](/details-gene/8740) signaling with a neutralizing monoclonal antibody could be a viable strategy to dampen pathological inflammation. Conversely, in the context of cancer immunotherapy, **activation** or supplementation of the [TNFSF14](/details-gene/8740) pathway, perhaps through an agonistic antibody or the administration of a recombinant form of the protein, could be explored to enhance anti-tumor T cell responses and overcome immune suppression within the tumor microenvironment.

Genular Protein ID: 3413089930

Symbol: TNF14_HUMAN

Name: Tumor necrosis factor ligand superfamily member 14

UniProtKB Accession Codes:

O43557 A8K7M2 C9J5H4 O75476 Q6FHA1 Q8WVF8 Q96LD2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 3 EvolutionaryTrace 1 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9462508

Title: LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator.

PubMed ID: 9462508

DOI: 10.1016/s1074-7613(00)80455-0

PubMed ID: 9765287

Title: Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth.

PubMed ID: 9765287

DOI: 10.1074/jbc.273.42.27548

PubMed ID: 11673523

Title: Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis.

PubMed ID: 11673523

DOI: 10.4049/jimmunol.167.9.5122

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 10754304

Title: LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response.

PubMed ID: 10754304

DOI: 10.4049/jimmunol.164.8.4105

Sequence Information:

  • Length: 240
  • Mass: 26350
  • Checksum: 49D0B1870F390B39
  • Sequence:
    • MEESVVRPSV FVVDGQTDIP FTRLGRSHRR QSCSVARVGL GLLLLLMGAG LAVQGWFLLQ 
LHWRLGEMVT RLPDGPAGSW EQLIQERRSH EVNPAAHLTG ANSSLTGSGG PLLWETQLGL 
AFLRGLSYHD GALVVTKAGY YYIYSKVQLG GVGCPLGLAS TITHGLYKRT PRYPEELELL 
VSQQSPCGRA TSSSRVWWDS SFLGGVVHLE AGEKVVVRVL DERLVRLRDG TRSYFGAFMV