Vtcn1-KO Mouse

Vtcn1, also known as B7-H4, B7S1, and B7x, is an immune checkpoint belonging to the B7 superfamily. It negatively regulates T-cell activation, influencing the immune response. This regulation is crucial in maintaining immune homeostasis, and dysregulation can lead to various diseases. The translational regulation of Vtcn1, with its transcript found in many tissues but protein expression restricted, indicates a complex regulatory mechanism [1].

Genetic deficiency of B7-H4 (Vtcn1) in allogeneic pregnancy models led to immune activation and fetal resorption, suggesting its role in onco-fetal immune tolerance [2]. In breast cancer, B7-H4 contributed to tumor progression, accompanied by CD8+ T cell exhaustion [2]. In ovarian carcinoma, low expression of Vtcn1 inhibited cell viability and metastasis both in vitro and in vivo, with cell cycle and JAK2/STAT pathways involved in this regulation [3]. In hepatocellular carcinoma, increased B7S1 (Vtcn1) expression on myeloid cells correlated with CD8+ T cell dysfunction, and its inhibition suppressed murine tumor development [4].

In summary, Vtcn1 is a key molecule in immune regulation, especially in T-cell activation. Through gene knockout-based studies in mouse models, its roles in onco-fetal immune tolerance, tumor progression in breast and liver cancers, and ovarian carcinoma cell behavior have been revealed. These findings highlight the potential of Vtcn1 as a therapeutic target in related disease areas.

References:

1. Vaishnav, Jayvadan, Khan, Farheen, Yadav, Madhu, Dwivedi, Mitesh, Begum, Rasheedunnisa. 2022. V-set domain containing T-cell activation inhibitor-1 (VTCN1): A potential target for the treatment of autoimmune diseases. In Immunobiology, 227, 152274. doi:10.1016/j.imbio.2022.152274. https://pubmed.ncbi.nlm.nih.gov/36095871/

2. Yu, Jiali, Yan, Yijian, Li, Shasha, Chen, Lieping, Zou, Weiping. 2024. Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance. In Cell, 187, 4713-4732.e19. doi:10.1016/j.cell.2024.06.012. https://pubmed.ncbi.nlm.nih.gov/38968937/

3. Gao, Aihua, Zhang, Liang, Chen, Xin, Liu, Yanan, Zhu, Weipei. 2015. Effect of VTCN1 on progression and metastasis of ovarian carcinoma in vitro and vivo. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 73, 129-34. doi:10.1016/j.biopha.2015.05.016. https://pubmed.ncbi.nlm.nih.gov/26211593/

4. Li, Jing, Lee, Younghee, Li, Yanjian, Ni, Ling, Dong, Chen. 2018. Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8+ T Cells. In Immunity, 48, 773-786.e5. doi:10.1016/j.immuni.2018.03.018. https://pubmed.ncbi.nlm.nih.gov/29625896/