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Numerous apoptosis\u2010related genes influence cell fate during T\u2010cell development. The PERP protein functions in apoptosis induction and as a tumor suppressor; however, p53 targets the\n                    <jats:italic>Perp<\/jats:italic>\n                    promoter, leading to its downregulation in various cancers. We investigated the specific role of\n                    <jats:italic>Perp<\/jats:italic>\n                    by studying conditional knock\u2010out mice exhibiting partial thymic T\u2010cell development defects and a significant accumulation of thymic CD4SP T\u2010cells. Ex\u00a0vivo and in\u00a0vivo analyses revealed that\n                    <jats:italic>Perp<\/jats:italic>\n                    regulates the survival of thymic T\u2010cell subsets during clonal deletion, particularly CD4SP T\u2010cells following TCR stimulation. These floxed mice also exhibited an expansion of the Helios\n                    <jats:sup>+<\/jats:sup>\n                    CD4SP thymocyte population. Moreover, middle\u2010aged floxed mice exhibited excessive accumulation of activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells in peripheral blood, alongside T cell\u2010mediated autoimmune arthritis. These findings indicate that conditional\n                    <jats:italic>Perp<\/jats:italic>\n                    knockout mice exhibit a deficiency in thymic negative selection and heightened susceptibility to autoimmunity with aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70514","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:10:48Z","timestamp":1776949848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Perp<\/i>\n                    Deficiency Induces Defective Negative Selection and Autoimmune Arthritis in Aged Mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Yan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Emergency West China Second University Hospital and Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Sichuan University  Chengdu 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of Chengdu Medical College Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 Hospital  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Deng","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College Chengdu Medical College  Chengdu China"},{"name":"Department of Pharmacology, School of Pharmacy Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-3394","authenticated-orcid":false,"given":"Guixiu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen 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 Chengdu China"},{"name":"Department of Immunology, School of Basic Medical Sciences Chengdu Medical College  Chengdu 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