B6-hTL1A (TNFSF15) Mouse

TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes ^[1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype ^[2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) ^[1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD ^[3-5].

The B6-hTL1A(TNFSF15) mouse is a humanized model constructed by replacing the mouse Tnfsf15 gene in situ with the human TNFSF15 gene using gene editing technology, in which the mouse Tnfsf15 endogenous extracellular domain will be replaced with the human TNFSF15 extracellular domain. The homozygous B6-hTL1A(TNFSF15) mice are viable and fertile, and can be used for studies on T cell differentiation and survival, immune response regulation, and pathogenesis of autoimmune diseases, as well as for TL1A-targeted drug development.