High-fat diet promotes exhaustion-associated T-cell remodeling across vascular and lymphoid tissues in atherosclerosis-prone mice

High-fat diet in ApoE-deficient mice increases exhaustion-associated T-cell states across vascular and lymphoid tissues, with the highest exhaustion scores in the aorta.

• Why it matters: Chronic dietary lipid exposure reshapes immune dysregulation in atherosclerosis, but it is unclear how T-cell states change across compartments and whether normalization fully restores them.
• What they did: ApoE-deficient mice were fed vegetarian diet or high-fat diet for 12 or 24 weeks, with a reversal group switched from high-fat to vegetarian; CD45+ single-cell RNA-seq with matched TCR-seq quantified exhaustion and naive programs.
• The result: After 24 weeks, exhausted-cell proportion was 15.7% under high-fat diet versus 10.6% under vegetarian diet, and reversal returned it to 10.6% while residual transcriptional changes persisted; aortic macrophages showed increased predicted T-cell communication and clonotype size correlated with exhaustion score (Spearman r = 0.57, p = 0.029).

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