Tnfsf15, also known as TL1A, is a member of the tumor necrosis factor family. It binds to death receptor 3 (DR3), providing co-stimulatory signals for activated lymphocytes, and is involved in modulating T-cell proliferation, cytokine production, and T-regulatory cell development and function. It participates in immunological pathways related to mucosal homeostasis, intestinal inflammation, and is also associated with angiogenesis regulation [1,3,4,5].

In dextran sodium sulfate (DSS)-induced chronic colitis mouse models, Tnfsf15 was up-regulated in gut-associated lymphoid tissue (GALT) along with death receptor 3, interferon-γ, and interleukin-17. Tnfsf15 enhanced both T-helper 1 (Th1) and T-helper 17 (Th17) effector functions, and neutralizing anti-Tnfsf15 antibodies prevented and attenuated chronic colitis by down-regulating Th1 and Th17 activation, suggesting its key role in chronic mucosal inflammation development [2].

In conclusion, Tnfsf15 is crucial in regulating immune responses, especially in mucosal immunity and chronic intestinal inflammation. Gene-knockout studies in mouse models, like those with DSS-induced colitis, have revealed its role in promoting chronic mucosal inflammation through modulating Th1 and Th17 activation, indicating its potential as a therapeutic target for diseases such as inflammatory bowel disease [2].

References:

1. Valatas, Vassilis, Kolios, George, Bamias, Giorgos. 2019. TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory System of Cytokines With Diverse Functions in Gut Mucosal Immunity. In Frontiers in immunology, 10, 583. doi:10.3389/fimmu.2019.00583. https://pubmed.ncbi.nlm.nih.gov/30972074/

2. Takedatsu, Hidetoshi, Michelsen, Kathrin S, Wei, Bo, Braun, Jonathan, Targan, Stephan R. 2008. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. In Gastroenterology, 135, 552-67. doi:10.1053/j.gastro.2008.04.037. https://pubmed.ncbi.nlm.nih.gov/18598698/

3. Xu, Wang-Dong, Li, Rong, Huang, An-Fang. 2022. Role of TL1A in Inflammatory Autoimmune Diseases: A Comprehensive Review. In Frontiers in immunology, 13, 891328. doi:10.3389/fimmu.2022.891328. https://pubmed.ncbi.nlm.nih.gov/35911746/

4. Schreiber, Taylor H, Podack, Eckhard R. . Immunobiology of TNFSF15 and TNFRSF25. In Immunologic research, 57, 3-11. doi:10.1007/s12026-013-8465-0. https://pubmed.ncbi.nlm.nih.gov/24242819/

5. Zhao, Huanyu, Zhang, Qiangzhe. . Signaling in TNFSF15-mediated Suppression of VEGF Production in Endothelial Cells. In Methods in molecular biology (Clifton, N.J.), 2248, 1-18. doi:10.1007/978-1-0716-1130-2_1. https://pubmed.ncbi.nlm.nih.gov/33185864/