Endothelial Elavl1 Is Required for CD8 T-Cell Persistence in Atherosclerosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Biology

Background:

• Atherosclerotic plaques involve lipid and immune cell accumulation.
• CD8 T cells are key players in cardiovascular disease severity.
• Endothelial cells' role in CD8 T cell activation and persistence is unclear.

Purpose of the Study:

• Investigate posttranscriptional regulation of CD8 T cell interactions by endothelial cells.
• Determine the impact of Elavl1 in endothelial cells on immune cell activity during atherosclerosis.

Main Methods:

• Utilized ribosomal profiling in RiboTRAP mice to analyze endothelial gene expression.
• Employed endothelial cell-specific knockout mice (CreERT2; Elavl ff; RiboTRAP) to study Elavl1 function.
• Performed in vitro assays to assess CD8 T cell persistence with Elavl1-deficient endothelial cells.

Main Results:

• Elavl1 motifs were enriched in transcripts with altered ribosomal association in atherosclerosis.
• Endothelial Elavl1 deletion enhanced atherogenic gene expression and reduced CD8 T cell accumulation by ~70%.
• Elavl1 deficiency impaired CD8 T cell persistence in vitro, independent of myeloid cells or antigen.

Conclusions:

• Endothelial Elavl1 acts as a suppressor, regulating CD8 T cell persistence in atherosclerosis.
• Endothelial cells can function as immune checkpoint-like regulators of CD8 T cells.
• Endothelial Elavl1 is a critical regulator of adaptive immunity in the context of atherosclerosis.