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CD8+ T Cells Drive Plaque Smooth Muscle Cell Dedifferentiation in Experimental Atherosclerosis
Sarah Schäfer1, Rajinikanth Gogiraju2, Melanie Rösch1
1Institute of Experimental Biomedicine (S.S., M.R., Y.K., L. Beck, J.G., C.C., A.Z.), University Hospital of Würzburg, Germany.
Arteriosclerosis, Thrombosis, and Vascular Biology
|June 13, 2024
Summary
CD8+ T cells influence smooth muscle cell (SMC) behavior in atherosclerosis, promoting dedifferentiation and adopting pro-calcifying, macrophage-like traits. Targeting these T cells may offer a therapeutic strategy for atherosclerotic lesion progression.
Area of Science:
- Immunology
- Cardiovascular Biology
- Cell Biology
Background:
- Atherosclerosis involves immune cells and smooth muscle cells (SMCs) in arterial lesions.
- CD8+ T cells are known to promote lesion growth but their role in advanced atherosclerosis is unclear.
Purpose of the Study:
- To investigate the role of CD8+ T cells in SMC phenotype modulation within established atherosclerotic lesions.
- To understand the impact of CD8+ T cells on SMC differentiation and function in advanced atherosclerosis.
Main Methods:
- Depletion of CD8+ T cells in low-density lipoprotein receptor-deficient mice with established atherosclerotic lesions.
- Single-cell RNA sequencing of aortic SMCs and coculture experiments with primary SMCs and CD8+ T cells.
Main Results:
- CD8+ T cell depletion increased SMC content and altered SMC gene expression, reducing contractile markers and increasing macrophage/osteoblast-like signatures.
- Activated CD8+ T cells induced SMC dedifferentiation, promoting macrophage and osteoblast-like phenotypes and triggering calcification.
- IFNγ-dependent induction of transcription factors like Runx1 in SMCs by CD8+ T cells was identified.
Conclusions:
- CD8+ T cells critically control SMC phenotype in atherosclerosis, driving dedifferentiation and pro-calcifying characteristics.
- CD8+ T cells promote SMCs to adopt macrophage-like and osteoblast-like phenotypes, contributing to atherosclerotic plaque development.
- Targeting CD8+ T cells presents a potential therapeutic strategy for managing atherosclerotic lesion progression.
