Tnfsf14, also known as LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells), is a member of the tumor necrosis factor superfamily. It plays a crucial role in immunological regulation, and is involved in pathways related to fibrosis, immune cell trafficking, and tissue homeostasis. It has significant biological importance in various physiological and pathological processes, and genetic models such as gene knockout mice have been valuable for studying its functions [1,2,3,4,5,6,7].

In gene knockout studies, Tnfsf14 -/- mice showed protection from ovariectomy-dependent bone loss, suggesting its role in mediating bone loss induced by estrogen deficiency [7]. Tnfsf14 deficiency in mice also accelerated browning in subcutaneous white adipose tissue during acute cold stress, indicating its function as an attenuator of beige fat biogenesis [6]. Additionally, in a study on adipose tissue phenotype, Tnfsf14 -/- and Rag -/-/Tnfsf14-(DKO) mice had lower visceral white adipose tissue weight, and DKO mice showed potential browning effects in inguinal white adipose tissue [5].

In conclusion, Tnfsf14 has diverse functions in biological processes such as bone metabolism, adipose tissue homeostasis, and immune regulation. Findings from Tnfsf14 KO mouse models have provided insights into its role in diseases like osteoporosis, obesity-related metabolic disorders, and potentially in cardiac fibrosis and atrial fibrillation, highlighting its significance as a potential therapeutic target in these disease areas [2,5,6,7].

References:

1. Skeate, Joseph G, Otsmaa, Mikk E, Prins, Ruben, Da Silva, Diane M, Kast, W Martin. 2020. TNFSF14: LIGHTing the Way for Effective Cancer Immunotherapy. In Frontiers in immunology, 11, 922. doi:10.3389/fimmu.2020.00922. https://pubmed.ncbi.nlm.nih.gov/32499782/

2. Wu, Yirong, Zhan, Siyao, Chen, Lian, Xu, Linhao, Xu, Yizhou. 2023. TNFSF14/LIGHT promotes cardiac fibrosis and atrial fibrillation vulnerability via PI3Kγ/SGK1 pathway-dependent M2 macrophage polarisation. In Journal of translational medicine, 21, 544. doi:10.1186/s12967-023-04381-3. https://pubmed.ncbi.nlm.nih.gov/37580750/

3. Zhang, Na, Liu, Xiaohong, Qin, Juliang, Liu, Mingyao, Du, Bing. 2023. LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 2575-2590. doi:10.1016/j.ymthe.2023.06.015. https://pubmed.ncbi.nlm.nih.gov/37408308/

4. Shi, Jia-Wei, Lai, Zhen-Zhen, Zhou, Wen-Jie, Zhao, Jian-Yuan, Li, Ming-Qing. 2024. TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence. In The EMBO journal, 43, 5018-5036. doi:10.1038/s44318-024-00220-3. https://pubmed.ncbi.nlm.nih.gov/39261664/

5. Oranger, Angela, Colaianni, Graziana, Ingravallo, Giuseppe, Colucci, Silvia, Brunetti, Giacomina. 2024. LIGHT/TNFSF14 Affects Adipose Tissue Phenotype. In International journal of molecular sciences, 25, . doi:10.3390/ijms25020716. https://pubmed.ncbi.nlm.nih.gov/38255789/

6. Kou, Yanbo, Liu, Qingya, Liu, Wenli, Liu, Zhuanzhuan, Wang, Yugang. 2018. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 1595-1604. doi:10.1096/fj.201800792R. https://pubmed.ncbi.nlm.nih.gov/30148680/

7. Brunetti, Giacomina, Storlino, Giuseppina, Oranger, Angela, Grano, Maria, Colucci, Silvia. 2020. LIGHT/TNFSF14 regulates estrogen deficiency-induced bone loss. In The Journal of pathology, 250, 440-451. doi:10.1002/path.5385. https://pubmed.ncbi.nlm.nih.gov/31990039/