{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:06:48Z","timestamp":1781672808241,"version":"3.54.5"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"52","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C7056\/A3110"],"award-info":[{"award-number":["C7056\/A3110"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C8624\/A4912"],"award-info":[{"award-number":["C8624\/A4912"]}],"id":[{"id":"10.13039\/501100000289","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":[[2019,12,26]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    In the present study, we provide evidence of a cellular mechanism of breach of tolerance in an in vivo model of spontaneous autoimmune thyroiditis (AIT). We observe that self-antigen (Ag) specific T\n                    <jats:sub>reg<\/jats:sub>\n                    circulate in all lymphatic tissues except for the lymph nodes (LNs) draining the thyroid, which represents the site of inflammation. By contrast, cognate effector T cells accumulate in the draining LNs and thyroid. The absence of T\n                    <jats:sub>reg<\/jats:sub>\n                    unleashes cognate T\n                    <jats:sub>eff<\/jats:sub>\n                    , which promote tissue destruction. We demonstrate that the organ-restricted disappearance of T\n                    <jats:sub>reg<\/jats:sub>\n                    is driven by the self-Ag, aberrantly expressed in a highly inflammatory environment, by a mechanism of activation-induced cell death.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1910281116","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T20:26:57Z","timestamp":1575923217000},"page":"26788-26797","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-6270","authenticated-orcid":false,"given":"Ester","family":"Badami","sequence":"first","affiliation":[{"name":"Cancer Research UK Oncology Unit, Cancer Sciences Division, University of Southampton, SO16 6YD Southampton, United Kingdom;"},{"name":"Fondazione Ricerca nel Mediterraneo (RiMED), 90133 Palermo, Italy;"},{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, Istituto di Ricovero e Cura a Carattere Scientifico\u2013Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, 90127 Palermo, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier N. F.","family":"Cexus","sequence":"additional","affiliation":[{"name":"Cancer Research UK Oncology Unit, Cancer Sciences Division, University of Southampton, SO16 6YD Southampton, United Kingdom;"},{"name":"Agency for Science Research and Technology, Institute of Molecular and Cell Biology, 138673 Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Quaratino","sequence":"additional","affiliation":[{"name":"Cancer Research UK Oncology Unit, Cancer Sciences Division, University of Southampton, SO16 6YD Southampton, United Kingdom;"},{"name":"Kymab, Babraham Research Campus, CB22 3AT Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1428"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1178"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni909"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0120-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2889"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.2.349"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1092"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00442"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.01.003"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases","volume":"155","author":"Sakaguchi S.","year":"1995","unstructured":"S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, M. Toda, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151\u20131164 (1995).","journal-title":"J. Immunol."},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.4049\/jimmunol.162.9.5317","article-title":"Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance","volume":"162","author":"Itoh M.","year":"1999","unstructured":"M. Itoh ., Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162, 5317\u20135326 (1999).","journal-title":"J. Immunol."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400810101"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni904"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1201"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00051"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.018"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00280-7"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni759"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2003.09.011"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6061"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.016"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611723113"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3871967"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7415"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3155"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12859"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1690"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01701"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.010"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12170"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/312639a0"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.06.029"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402990"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12398"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.022"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902379"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22010134"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.105"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14185"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00204-X"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3025"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0468"},{"key":"e_1_3_3_45_2","unstructured":"O. Cexus \u201cImmunological mechanisms controlling chronic inflammatory diseases \u201d PhD thesis University of Southampton Southampton UK (2009)."},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085650"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1910281116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1910281116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T16:21:24Z","timestamp":1695486084000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1910281116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":46,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2019,12,26]]}},"alternative-id":["10.1073\/pnas.1910281116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1910281116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]},"assertion":[{"value":"2019-12-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}