Aortic & peripheral vascular disease
Ezh2 Shapes T Cell Plasticity to Drive Atherosclerosis
Authors' conclusion
Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis.
Study context
- Population
- Human carotid endarterectomy specimens; atherosclerosis-prone Apoe-deficient mice
- Comparison
- T cell-specific Ezh2 deletion vs Ezh2-intact, in Apoe-deficient mice
Main finding
As reported in the abstract
- EZH2 expression elevated in advanced human atherosclerotic plaques, primarily in the T cell nucleus
- Ezh2cd4-KO, but not Ezh2cd8-KO, mice showed reduced atherosclerosis with fewer advanced plaques, containing less collagen and macrophages
- Ezh2 absence in CD4+ T cells: type 2 immune response with increased Il-4 gene and protein expression in aorta and lymphoid organs
- In vitro, Ezh2-deficient T cells polarized macrophages toward an anti-inflammatory phenotype
- scRNA-seq of splenic T cells: Ezh2 deficiency reduced naive, Ccl5+ and regulatory T cells; increased memory T cells and invariant natural killer T (iNKT) cells
- Flow cytometry: shift toward Th2 effector CD4+ T cells and profound increase in splenic iNKT cells with increased Plzf (iNKT2 marker) in Ezh2cd4-KO mice
- Zbtb16 transcripts elevated in aorta of Ezh2cd4-KO mice, suggesting iNKT2 accumulation in plaque
- H3K27me3-ChIP-qPCR: T cell-Ezh2 regulates transcription of Il-4 and Zbtb16 genes
Original publication
Ezh2 Shapes T Cell Plasticity to Drive Atherosclerosis. Circulation. Published 7 February 2025. doi:10.
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