TL1A

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Ligands
TL1A (Human)

GtoPdb Ligand ID: 5071

Synonyms: Tumor necrosis factor ligand superfamily member 15, membrane form

Compound class: Endogenous peptide in human, mouse or rat

Comment: TL1A occurs as both membrane‐bound and soluble forms. It principally functions as a negative modulator of epithelial cell proliferation.
Inhibiting the TL1A/death receptor 3 (TNFRSF25) pathway has been proposed as mechanism to treat inflammatory bowel disease [1]. In addition, TL1A has been associated with tumourigenesis and progression of some gastrointestinal malignancies [4,7,11], making it a target of interest for the development of novel anti-cancer drugs, and profibrotic processes.
TL1A is also an endogenous ligand for decoy receptor 3 (DcR3; TNFRSF6B).

Species: Human

Immunopharmacology Comments
TNF-like ligand 1A (TL1A; TNFSF15) is a TNF family cytokine that is expressed by endotheial cells. It is not expressed by T or B cells. Acting as a ligand for both the death receptor 3 (DR3; TNFRSF25) and decoy receptor 3 (DcR3; TNFRSF6B) it is able activate the NF-κB and MAPK signalling pathways, and it induces fibrogenesis. The TL1A/DR3/DcR3 axis regulates mucosal immunity and inflammation. Overexpression and naturally ocurring polymorphisms in the TNFSF15 gene strongly associate with inflammatory bowel disease [6,8]. Blocking the TL1A/DR3 pathway (which inhibits Th1 and Th17 cell responses and profibrotic pathways, and increases regulatory T cell activity) is a therapeutic mechanism that is proposed for the treament of chronic inflammatory conditions, and fibrotic liver and lung diseases. Several clinical candidate monoclonal antibodies that neutralise TL1A are in clinical development; afimkibart (also known as PF-06480605, RVT-3101, or RG6631) [1-2], duvakitug (TEV48574) [10] and tulisokibart (PRA023) [3]. An anti-DR3 antibody (SL-325) is also in clinical development [5].

Immunopharmacology Comments

TNF-like ligand 1A (TL1A; TNFSF15) is a TNF family cytokine that is expressed by endotheial cells. It is not expressed by T or B cells. Acting as a ligand for both the death receptor 3 (DR3; TNFRSF25) and decoy receptor 3 (DcR3; TNFRSF6B) it is able activate the NF-κB and MAPK signalling pathways, and it induces fibrogenesis. The TL1A/DR3/DcR3 axis regulates mucosal immunity and inflammation.

Overexpression and naturally ocurring polymorphisms in the TNFSF15 gene strongly associate with inflammatory bowel disease [6,8].

Blocking the TL1A/DR3 pathway (which inhibits Th1 and Th17 cell responses and profibrotic pathways, and increases regulatory T cell activity) is a therapeutic mechanism that is proposed for the treament of chronic inflammatory conditions, and fibrotic liver and lung diseases. Several clinical candidate monoclonal antibodies that neutralise TL1A are in clinical development; afimkibart (also known as PF-06480605, RVT-3101, or RG6631) [1-2], duvakitug (TEV48574) [10] and tulisokibart (PRA023) [3]. An anti-DR3 antibody (SL-325) is also in clinical development [5].