{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:59:48Z","timestamp":1784293188978,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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 <jats:italic>Apoe<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice, which was attributed to increased macrophage recruitment and increased CD8<jats:sup>+<\/jats:sup> T cell activation in the plaque.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To further study the T cell specific role of CBL-B in atherosclerosis, <jats:italic>Apoe<jats:sup>-\/-<\/jats:sup><\/jats:italic> CD4<jats:sup>cre<\/jats:sup><jats:italic>Cblb<\/jats:italic><jats:sup>fl\/fl<\/jats:sup> (Cbl-b<jats:sup>cKO<\/jats:sup>) mice and <jats:italic>Apoe<jats:sup>-\/-<\/jats:sup>CD4<jats:sup>WT<\/jats:sup><\/jats:italic>Cblb<jats:sup>fl\/fl<\/jats:sup> littermates (Cbl-b<jats:sup>fl\/fl<\/jats:sup>) were fed a high cholesterol diet for ten weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cbl-b<jats:sup>cKO<\/jats:sup> mice had smaller atherosclerotic lesions in the aortic arch and root compared to Cbl-b<jats:sup>fl\/fl<\/jats:sup>, and a substantial increase in CD3<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells and a 1.8-fold increase in regulatory T cells in the spleen. Splenic CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells had increased expression of C-X-C Motif Chemokine Receptor 3 (CXCR3) and interferon-\u03b3 (IFN-\u03b3), indicating a T helper 1 (Th1)-like\/effector CD8<jats:sup>+<\/jats:sup> T cell-like phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, Cbl-b<jats:sup>cKO<\/jats:sup> mice have reduced atherosclerosis but show increased T cell accumulation in the plaque accompanied by systemic T cell activation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1297893","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:20:37Z","timestamp":1709526037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["T cell specific deletion of Casitas B lineage lymphoma-b reduces atherosclerosis, but increases plaque T cell infiltration and systemic T cell 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