{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:17:57Z","timestamp":1781108277472,"version":"3.54.1"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI121367"],"award-info":[{"award-number":["R01AI121367"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R25GM130437"],"award-info":[{"award-number":["R25GM130437"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,4]]},"abstract":"<jats:p>\n                    Thymic stromal cells (TSCs) are critical regulators of T cell tolerance, but their basic biology has remained under-characterized because they are relatively rare and difficult to isolate. Recent work has revealed that constitutive autophagy in TSCs is required for self-antigen presentation and central T cell tolerance induction; however, the mechanisms regulating constitutive autophagy in TSCs are not well understood. Hydrogen peroxide has been shown to increase autophagy flux in other tissues, and we previously identified conspicuously low expression of the hydrogen peroxide\u2013quenching enzyme catalase in TSCs. We investigated whether the redox status of TSCs established by low catalase expression regulates their basal autophagy levels and their capacity to impose central T cell tolerance. Transgenic overexpression of catalase diminished autophagy in TSCs and impaired thymocyte clonal deletion, concomitant with increased frequencies of spontaneous lymphocytic infiltrates in lung and liver and of serum antinuclear antigen reactivity. Effects on clonal deletion and autoimmune indicators were diminished in catalase transgenic mice when autophagy was rescued by expression of the Becn1\n                    <jats:sup>F121A\/F121A<\/jats:sup>\n                    knock-in allele. These results suggest a metabolic mechanism by which the redox status of TSCs may regulate central T cell tolerance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2204296119","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T15:21:09Z","timestamp":1664205669000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Redox status regulates autophagy in thymic stromal cells and promotes T cell tolerance"],"prefix":"10.1073","volume":"119","author":[{"given":"Manpreet K.","family":"Semwal","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"},{"name":"Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison K.","family":"Hester","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"},{"name":"Department of Medicine, Blood and Marrow Transplantation Division, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangming","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chioma","family":"Udeaja","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Cepeda","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-8497","authenticated-orcid":false,"suffix":"II","given":"John S.","family":"Verschelde","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-4672","authenticated-orcid":false,"given":"Sarah A.","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-5406","authenticated-orcid":false,"given":"Simon","family":"Emtage","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kymberly","family":"Wimberly","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-0222","authenticated-orcid":false,"given":"Ann V.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.09.010"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.2.730"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.024"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.008"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.12.022"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636072"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.2.127"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/36.5.2895787"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115715"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.04.198"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120358109"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08040"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3801"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014819832003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.7.12754"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.150"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601623"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2007.07.009"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.3.3.12106"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25178"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13321"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402233"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-09-0704"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07208"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122149"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106653"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.19496"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061303"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0162-7"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45917-2"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013040374"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1766"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71769"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900191"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.95"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00398"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.12.011"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906956106"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040643"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104904"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.009"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3667"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1385"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082449"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601516"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09727-4"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.007"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71578"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082232"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.1A0921-502RR"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16081-3"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323616"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.372"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00267-4"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161864"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.020"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080866"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.10.018"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.01.016"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110363"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2204296119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T15:27:16Z","timestamp":1664206036000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2204296119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":62,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2022,10,4]]}},"alternative-id":["10.1073\/pnas.2204296119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2204296119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]},"assertion":[{"value":"2022-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2204296119"}}