Vsir, also known as V-domain immunoglobulin suppressor of T cell activation (VISTA), is a crucial immune checkpoint molecule. It inhibits T cell effector function and maintains peripheral tolerance, playing a significant role in the immune response [2,4].

In Vsir-/-mice, psoriasis-like skin inflammation is exacerbated. Single-cell RNA-seq analysis of the skin in these mice identified 12 major cell subtypes. Macrophages were the main immune cell population, and an expansion of DCs and fibroblasts was observed in Vsir-/-psoriatic mice. Gene expression analysis revealed upregulation of Hspb1 and Cebpb, and differential gene expression and gene ontology enrichment analyses uncovered specific gene expression patterns and putative functions of each cell type, suggesting a role for Vsir in psoriasis [1].

In acute myeloid leukemia (AML), higher VSIR expression is associated with significantly shorter survival, and it can predict progression from myelodysplastic syndromes (MDS) to AML, indicating its potential role in the early stage of AML development [2].

In glycogen storage disease type Ib (GSD-Ib) patients with inflammatory bowel disease (IBD), hyper-activation of the CCL4L2-VSIR axis leads to unique IBD progression, suggesting a microbiota-driven pathomechanism [3].

In conclusion, Vsir is an important immune checkpoint gene. Studies using Vsir-/-mouse models have revealed its role in diseases such as psoriasis, AML, and GSD-Ib-associated IBD. These findings provide insights into the mechanisms of these diseases and potential therapeutic targets related to Vsir.