Vsir, also known as V-domain immunoglobulin suppressor of T cell activation (VISTA), is a key immune checkpoint molecule. It plays a crucial role in inhibiting T cell effector function and maintaining peripheral tolerance, thus being involved in immune-related pathways [2,4]. The study of Vsir-related genetic models, such as Vsir-/-mice, is valuable for understanding its functions.

In Vsir-/-mice, exacerbated psoriasis-like skin inflammation occurs. Single-cell RNA-seq analysis shows an expansion of DCs and fibroblasts, along with specific gene expression changes like upregulation of Hspb1 and Cebpb. These findings uncover the transcriptional landscape and phenotypic heterogeneity of skin macrophages in psoriasis [1]. In acute myeloid leukemia (AML), higher VSIR expression predicts shorter survival, and it can also predict progression from myelodysplastic syndromes (MDS) to AML [2]. In glycogen storage disease type Ib (GSD-Ib), hyper-activation of the CCL4L2-VSIR axis in colonic epithelial cells mediates the unique progression of inflammatory bowel disease (IBD) [3].

In conclusion, Vsir is essential in immune regulation. Gene-knockout mouse models, especially Vsir-/-mice, have revealed its roles in diseases like psoriasis, AML, MDS, and IBD associated with GSD-Ib. These studies help understand the underlying mechanisms and may offer potential therapeutic targets for these diseases.

References:

1. Qie, Chenxin, Jiang, Jingwei, Liu, Wanmei, Xie, Xiaoxue, Liu, Jun. 2020. Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of skin macrophages in Vsir-/- murine psoriasis. In Theranostics, 10, 10483-10497. doi:10.7150/thno.45614. https://pubmed.ncbi.nlm.nih.gov/32929361/

2. Yao, Kevin, Zhou, Emily, Schaafsma, Evelien, Zhang, Baoyi, Cheng, Chao. 2022. Immune checkpoint gene VSIR predicts patient prognosis in acute myeloid leukemia and myelodysplastic syndromes. In Cancer medicine, 12, 5590-5602. doi:10.1002/cam4.5409. https://pubmed.ncbi.nlm.nih.gov/36394080/

3. Lan, Jiaoli, Zhang, Yuxin, Jin, Cuiyuan, Guo, Yuxiong, Yang, Min. 2024. Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2309471. doi:10.1002/advs.202309471. https://pubmed.ncbi.nlm.nih.gov/38889269/

4. Liu, Yuanyuan, Zhang, Jingwei, Wang, Zeyu, Yang, Tubao, Cheng, Quan. 2022. Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis. In Frontiers in cell and developmental biology, 10, 821649. doi:10.3389/fcell.2022.821649. https://pubmed.ncbi.nlm.nih.gov/35493077/