Deciphering the Role of VSIG-3 as a VISTA Ligand in Human T-Cell Regulation

3 June 2024
The B7 family and their receptors are integral in modulating T-cell responses, offering potential targets for immunotherapy. This study uncovers a new interaction between VSIG-3/IGSF11 and the B7 family member VISTA/PD-1H, which suppresses human T-cell functions through a novel pathway. An extensive ELISA binding screening assay identified a specific binding between VSIG-3 and VISTA, with no observed interaction with other B7 family members under the same conditions. Notably, VSIG-8 was found to have no significant interaction with VISTA.

VSIG-3 has been shown to inhibit T-cell proliferation even in the presence of T-cell receptor signaling and to markedly reduce the production of various cytokines and chemokines by human T cells. Anti-VISTA neutralization antibodies were found to mitigate the binding between VSIG-3 and VISTA, as well as the T-cell inhibition induced by VSIG-3.

The identification of VSIG-3 as a ligand for VISTA that can suppress human T-cell proliferation and cytokine production presents a new co-inhibitory pathway. This discovery could pave the way for new therapeutic strategies for a range of conditions, including cancer, autoimmune diseases, infections, and transplant rejection, and may also contribute to the development of more effective vaccines.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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