Tumor necrosis factor ligand superfamily member 15 (TNFSF15) (TL1A)

TNF-like ligand 1A (TL1A), also known as Tumor Necrosis Factor Ligand Superfamily Member 15 (TNFSF15), is a cytokine that plays a central role in modulating both innate and adaptive immune responses (7.3.1, 7.5.1). It is primarily expressed by endothelial cells and antigen-presenting cells, such as macrophages and dendritic cells, and its expression is significantly upregulated in response to inflammatory stimuli (7.3.3, 7.4.5). TL1A exerts its biological effects by binding to its functional receptor, Death Receptor 3 (DR3), which is mainly found on activated T cells and innate lymphoid cells (7.3.3, 7.5.3). This interaction serves as a potent co-stimulatory signal that drives the production of pro-inflammatory cytokines and promotes Th1 and Th17 cell differentiation (7.1.1, 7.5.1). Beyond its role in acute inflammation, TL1A is a critical driver of tissue remodeling and fibrosis, distinguishing it from other TNF superfamily members (7.2.2, 7.2.5). Dysregulation of the TL1A/DR3 axis is strongly linked to the pathogenesis of various autoimmune and inflammatory diseases, most notably inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (7.1.3, 7.3.2). Genetic studies have identified polymorphisms in the TNFSF15 gene that correlate with disease susceptibility and severity (7.1.1, 7.5.2). Consequently, TL1A has emerged as a high-priority therapeutic target, with several monoclonal antibodies like tulisokibart and afimkibart in clinical development (7.2.4, 8.1.2). These therapies aim to neutralize TL1A to suppress chronic inflammation and prevent fibrotic complications, offering a potential breakthrough for patients who are refractory to existing biologics (7.2.5, 8.1.4).

Other names

TNF-like ligand 1AVascular endothelial growth inhibitorVEGITL1TNF ligand-related molecule 1TNLG1B

Neutralization of TL1A ligand to prevent binding to its functional receptor DR3 and decoy receptor DcR3, thereby inhibiting pro-inflammatory and pro-fibrotic signaling pathways.