huDR3(TNFRSF25) Mouse

Tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3), is a member of the tumor necrosis factor receptor (TNFR) superfamily and serves as the specific receptor for TNFSF15 (TL1A). It plays a critical role in immune homeostasis regulation, inflammatory responses, and apoptosis. This receptor contains a death domain and can specifically bind to its ligand TL1A. Upon binding, it recruits downstream adaptor molecules to activate NF-κB and MAPK signaling pathways, or induce apoptosis, thereby participating in the regulation of T cell proliferation and differentiation—particularly Th2 and Th17 cells—regulatory T cell (Treg) expansion, and tissue inflammatory responses ^[1]. TNFRSF25 is primarily expressed in lymphocyte-rich tissues, such as the spleen, thymus, and lymph nodes. It is highly expressed on the surface of activated T cells, NKT cells, and certain innate lymphoid cells, and can also be detected in mucosal tissues such as the intestine and lungs, suggesting its important role in mucosal immunity and inflammation regulation ^[2].

Abnormal activation of the TNFRSF25/TL1A signaling pathway is closely associated with the development of various inflammatory and autoimmune diseases, with particularly prominent roles in inflammatory bowel disease (IBD), allergic asthma, and psoriasis. Studies have shown that in inflammatory bowel disease, TNFRSF25 signaling promotes Th17 cell activation and amplifies intestinal inflammation, and is also involved in fibrosis processes. In allergic asthma, this pathway enhances Th2-type immune responses and airway inflammation ^[1,3]. Based on its critical role in immune regulation, TNFRSF25 has become a highly promising therapeutic target in the field of immunotherapy for inflammatory and autoimmune diseases. Anti-TL1A monoclonal antibodies have demonstrated favorable efficacy in clinical trials for IBD ^[4-5].

huDR3(TNFRSF25) mice are humanized models constructed using gene editing technology. In this model, the sequences from the ATG start codon to the TGA stop codon of the mouse Tnfrsf25 gene were replaced with the sequences from the ATG start codon to the TGA stop codon of the human TNFRSF25 gene. huDR3(TNFRSF25) mice can be used for preclinical studies on the pathogenesis of autoimmune and inflammatory diseases, such as inflammatory bowel disease (IBD), allergic asthma, and psoriasis, as well as for the evaluation of DR3-targeted drugs.