{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:33Z","timestamp":1753890573666,"version":"3.41.2"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["360043781","397484323"],"award-info":[{"award-number":["360043781","397484323"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL115232","HL121697","HL88093"],"award-info":[{"award-number":["HL115232","HL121697","HL88093"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Atherosclerosis is a chronic, lipid-driven disease of medium sized arteries which causes myocardial infarction and stroke. Recently, an adaptive immune response against the plaque-associated autoantigen Apolipoprotein B100 (ApoB), the structural protein component of low-density lipoprotein, has been implicated in atherogenesis. In healthy individuals, CD4<jats:sup>+<\/jats:sup>T cells responding to ApoB mainly comprised regulatory T cells, which confer immune tolerance and atheroprotection. Mice and patients with atherosclerosis harbor increased numbers of proatherogenic ApoB-reactive T-helper cell subsets. Given the lack of therapies targeting proatherogenic immunity, clarification of the underlying mechanisms is of high clinical relevance. T cells develop in the thymus, where strong autoreactive T cells are eliminated in the process of negative selection. Herein, we investigated whether the transcription factor autoimmune regulator (AIRE), which controls expression of numerous tissue-restricted self-antigens in the thymus, is involved in mediating tolerance to ApoB and whether<jats:italic>Aire<\/jats:italic>deficiency might contribute to atherogenesis. Mice deficient for<jats:italic>Aire<\/jats:italic>were crossbred to apolipoprotein E-deficient mice to obtain atherosclerosis-prone<jats:italic>Aire<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, which were fed a regular chow diet (CD) or western-type diet (WD). CD4<jats:sup>+<\/jats:sup>T cells responding to the ApoB peptide p6 were analyzed by flow cytometry. We demonstrate that<jats:italic>Aire<\/jats:italic>deficiency influences neither generation nor activation of ApoB-reactive T cells and has only minor and overall inconsistent impacts on their phenotype. Furthermore, we show that atherosclerotic plaque size is not affected in<jats:italic>Aire<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>compared to<jats:italic>Aire<\/jats:italic><jats:sup>+\/+<\/jats:sup><jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>, irrespective of diet and gender. In conclusion, our data suggests that AIRE is not involved in regulating thymic expression of ApoB or atherosclerosis. Alternative mechanisms how ApoB-reactive CD4 T cells are selected in the thymus will have to be investigated.<\/jats:p>","DOI":"10.3389\/fcvm.2021.812769","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T05:15:07Z","timestamp":1642050907000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Autoimmune Regulator (AIRE) Deficiency Does Not Affect Atherosclerosis and CD4 T Cell Immune Tolerance to Apolipoprotein B"],"prefix":"10.3389","volume":"8","author":[{"given":"Felix 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