TNF-α drives pancreatic microcirculatory dysfunction via CD8+ T cell-mediated endothelial injury in severe acute pancreatitis

To investigate the role of CD8+ T cells and TNF-α in endothelial damage and microcirculatory dysfunction in severe acute pancreatitis (SAP).

Patient Cohorts: The study analyzed pancreatic tissues from 8 patients with SAP and 13 patients with pancreatic tumors, as well as blood samples from 153 patients with SAP.
Single-Cell RNA Sequencing: scRNA-seq was performed on pancreatic tissues to reconstruct the cellular landscape and identify key factors influencing SAP pathophysiology.

Infiltrating CD8+ T cells directly target and kill endothelial cells via the NKG2D–UL16-binding proteins (ULBPs) axis.
TNF-α amplifies CD8+ T cell cytotoxicity by inducing ULBPs expression on endothelium.
TNF-α is a biomarker of disease severity and a potential therapeutic target for SAP.

The study highlights the role of CD8+ T cells and TNF-α in microcirculatory failure in SAP.

The study relies on a limited number of patient samples, which may affect the generalizability of the findings.
The research is primarily based on scRNA-seq data, which may not capture all relevant cellular interactions in vivo.

The findings indicate the involvement of TNF-α in microcirculatory dysfunction in SAP.