Tnfsf14, also known as LIGHT (Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells), is a crucial member of the tumor necrosis factor superfamily. It is involved in immunological regulation and fibrosis-related pathways. LIGHT is expressed in inflammatory effector cells and plays an important role in various biological processes, including immune-tumor interactions, tissue fibrosis, and metabolic regulation [1-10]. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, Tnfsf14-deficient (Tnfsf14-/-) mice are protected from ovariectomy-dependent bone loss, suggesting that LIGHT mediates bone loss induced by estrogen deficiency [2]. In adipose tissue studies, LIGHT deficiency in mice promoted obesity during high-fat diet feeding and accelerated browning in the subcutaneous white adipose tissue during acute cold stress, indicating its role in regulating adipose tissue homeostasis [3]. In the context of cancer, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells showed enhanced anti-tumor efficacy and infiltration compared to conventional CAR-T cells, revealing its potential in reconstituting a high immune-infiltrated tumor microenvironment [1].

In conclusion, Tnfsf14 is essential in multiple biological processes. Model-based research, especially using Tnfsf14 KO mouse models, has revealed its roles in diseases such as postmenopausal osteoporosis, obesity-related metabolic disorders, and cancer. These findings contribute to understanding disease mechanisms and may offer potential therapeutic targets for these conditions.

References:

1. 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/

2. 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/

3. 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/