| First Author | Vos WG | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1297893 | PubMed ID | 38504977 |
| Mgi Jnum | J:347518 | Mgi Id | MGI:7615431 |
| Doi | 10.3389/fimmu.2024.1297893 | Citation | Vos WG, et al. (2024) T cell specific deletion of Casitas B lineage lymphoma-b reduces atherosclerosis, but increases plaque T cell infiltration and systemic T cell activation. Front Immunol 15:1297893 |
| abstractText | INTRODUCTION: Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall, and the underlying cause of the majority of cardiovascular diseases. Recent advances in high-parametric immunophenotyping of immune cells indicate that T cells constitute the major leukocyte population in the atherosclerotic plaque. The E3 ubiquitin ligase Casitas B-lymphoma proto-oncogene-B (CBL-B) is a critical intracellular regulator that sets the threshold for T cell activation, making CBL-B a potential therapeutic target to modulate inflammation in atherosclerosis. We previously demonstrated that complete knock-out of CBL-B aggravated atherosclerosis in Apoe(-/-) mice, which was attributed to increased macrophage recruitment and increased CD8(+) T cell activation in the plaque. METHODS: To further study the T cell specific role of CBL-B in atherosclerosis, Apoe(-/-) CD4(cre) Cblb (fl/fl) (Cbl-b(cKO)) mice and Apoe(-/-)CD4(WT)Cblb(fl/fl) littermates (Cbl-b(fl/fl)) were fed a high cholesterol diet for ten weeks. RESULTS: Cbl-b(cKO) mice had smaller atherosclerotic lesions in the aortic arch and root compared to Cbl-b(fl/fl), and a substantial increase in CD3(+) T cells in the plaque. Collagen content in the plaque was decreased, while other plaque characteristics including plaque necrotic core, macrophage content, and smooth muscle cell content, remained unchanged. Mice lacking T cell CBL-B had a 1.4-fold increase in CD8(+) T cells and a 1.8-fold increase in regulatory T cells in the spleen. Splenic CD4(+) and CD8(+) T cells had increased expression of C-X-C Motif Chemokine Receptor 3 (CXCR3) and interferon-gamma (IFN-gamma), indicating a T helper 1 (Th1)-like/effector CD8(+) T cell-like phenotype. CONCLUSION: In conclusion, Cbl-b(cKO) mice have reduced atherosclerosis but show increased T cell accumulation in the plaque accompanied by systemic T cell activation. |
