V-domain Ig Suppressor of T cell Activation Expression During Hemorrhage or Sepsis-Induced Acute Respiratory Distress Syndrome: Insights From a Mouse Model.

Summary

In a hemorrhage plus sepsis mouse model of indirect ARDS, VISTA expression increased across monocytes, macrophages, neutrophils, and pulmonary epithelial/endothelial cells. The study supports VISTA as a candidate biomarker and potential immunotherapeutic target for ARDS.

Key Findings

• Hemorrhage+CLP induced systemic and pulmonary inflammation consistent with indirect ARDS.
• VISTA expression was upregulated on blood monocytes, lung macrophages, circulating and lung-infiltrating neutrophils.
• Pulmonary epithelial and endothelial cells also showed increased VISTA expression, suggesting parenchymal involvement.

Clinical Implications

No immediate change to practice; however, VISTA measurement or modulation could inform future risk stratification and targeted therapies in ARDS if validated in humans.

Limitations

• Preclinical mouse data with no functional manipulation of VISTA (e.g., blockade or knockout).
• Lack of human validation and limited to a single ARDS model.

Future Directions

Test VISTA blockade/agonism or genetic models to define causality; validate VISTA as a biomarker in human ARDS cohorts; explore timing and cell-specific targeting.