{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:48:23Z","timestamp":1791355703233,"version":"4.3.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The tumor suppressor p53 plays a central role in tumor suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair. In addition to the antitumor functions of p53, accumulating evidence using systemic p53-deficient mice suggests that p53 suppresses autoimmunity. However, it remains unknown how p53 suppresses autoimmunity. In this study, we generated T cell\u2013specific p53-deficient mice (CD4-Cre p53fl\/fl mice, or p53 conditional knockout [cKO] mice) and found that aged p53-cKO mice spontaneously developed inflammatory lesions in various organs, including lung, liver, stomach, thyroid gland, submandibular gland, and kidney. Additionally, anti-nuclear Abs and autoantibodies against gastric parietal cells were detected in p53-cKO mice but not in control p53fl\/fl mice (p53 wild-type mice). Importantly, the number of Foxp3+CD4+ regulatory T cells (Tregs) in the spleen and lung as well as in vitro differentiation of induced Tregs was significantly reduced in p53-cKO mice as compared with that in p53 wild-type mice. Regarding the mechanisms underlying p53-mediated Treg induction, p53 enhanced the transcription of Foxp3 by binding to the promoter and the conserved noncoding DNA sequence-2 of the Foxp3 gene. Taken together, these results suggest that p53 expressed in T cells functions as a suppressor for autoimmunity by inducing Treg differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.1300509","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T04:46:35Z","timestamp":1378356395000},"page":"3614-3623","source":"Crossref","is-referenced-by-count":78,"title":["Tumor Suppressor p53 Inhibits Systemic Autoimmune Diseases by Inducing Regulatory T Cells"],"prefix":"10.1093","volume":"191","author":[{"given":"Hirotoshi","family":"Kawashima","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Takatori","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arifumi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Minamino","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences , Niigata 951-8510,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,1]]},"reference":[{"key":"2025032405420412400_r1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.cell.2009.04.037","article-title":"Blinded by the light: the growing complexity of p53","volume":"137","author":"Vousden","year":"2009","journal-title":"Cell"},{"key":"2025032405420412400_r2","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/nature07986","article-title":"Cytoplasmic functions of the tumour suppressor p53","volume":"458","author":"Green","year":"2009","journal-title":"Nature"},{"key":"2025032405420412400_r3","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1002\/eji.200425371","article-title":"Monoclonal antibody to a DNA-binding domain of p53 mimics charge structure of DNA: anti-idiotypes to the anti-p53 antibody are anti-DNA","volume":"34","author":"Herkel","year":"2004","journal-title":"Eur. 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