{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:48:00Z","timestamp":1747187280509,"version":"3.40.5"},"reference-count":103,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007885","name":"European Association for the Study of Diabetes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011103","name":"Sixth Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006673","name":"Fonds L\u00e9on Fredericq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Confirming Burnet's early hypothesis, elimination of self\u2010reactive T cells in the thymus was demonstrated in the late 1980s, and an important question immediately arose about the nature of the self\u2010peptides expressed in the thymus. Many genes encoding neuroendocrine\u2010related and tissue\u2010restricted antigens (TRAs) are transcribed in thymic epithelial cells (TECs). They are then processed for presentation by proteins of the major histocompatibility complex (MHC) expressed by TECs and thymic dendritic cells. MHC presentation of self\u2010peptides in the thymus programs self\u2010tolerance by two complementary mechanisms: (1) negative selection of self\u2010reactive \u201cforbidden\u201d T cell clones starting already in fetal life, and (2) generation of self\u2010specific thymic regulatory T lymphocytes (tT<jats:sub>reg<\/jats:sub> cells), mainly after birth. Many studies, including the discovery of the transcription factors autoimmune regulator (AIRE) and fasciculation and elongation protein zeta family zinc finger (FEZF2), have shown that a defect in thymus central self\u2010tolerance is the earliest event promoting autoimmunity. AIRE and FEZF2 control the level of transcription of many neuroendocrine self\u2010peptides and TRAs in the thymic epithelium. Furthermore, <jats:italic>AIRE<\/jats:italic> and <jats:italic>FEZF2<\/jats:italic> mutations are associated with the development of autoimmunity in peripheral organs. The discovery of the intrathymic presentation of self\u2010peptides has revolutionized our knowledge of immunology and is opening novel avenues for prevention\/treatment of autoimmunity.<\/jats:p>","DOI":"10.1111\/nyas.14089","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T12:04:53Z","timestamp":1555934693000},"page":"113-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The presentation of neuroendocrine self\u2010peptides in the thymus: an essential event for individual life and vertebrate survival"],"prefix":"10.1111","volume":"1455","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-7284","authenticated-orcid":false,"given":"Vincent","family":"Geenen","sequence":"first","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Trussart","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Michaux","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aymen","family":"Halouani","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"},{"name":"Faculty of Sciences and Faculty of Pharmacy University of Tunis El Manar  Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hela","family":"Ja\u00efdane","sequence":"additional","affiliation":[{"name":"Faculty of Sciences and Faculty of Pharmacy University of Tunis El Manar  Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Coll\u00e9e","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Renard","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Daukandt","sequence":"additional","affiliation":[{"name":"X\u2010Press Biologics Industrial Park of Milmort  Li\u00e8ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Ledent","sequence":"additional","affiliation":[{"name":"X\u2010Press Biologics Industrial Park of Milmort  Li\u00e8ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri","family":"Martens","sequence":"additional","affiliation":[{"name":"GIGA Institute University of Li\u00e8ge  Li\u00e8ge\u2010Sart Tilman Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20173306024"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","unstructured":"Geenen V.&W.Savino.2019.History of the thymus\u2014from a vestigial organ to the programming of immunological self\u2010tolerance. InThymus Transcriptome and Cell Biology.G.A.Passos Ed.London:Springer\u2010Nature.","DOI":"10.1007\/978-3-030-12040-5_1"},{"key":"e_1_2_10_4_1","first-page":"474","article-title":"The development and probable function of the thymus","volume":"9","author":"Beard J.","year":"1894","journal-title":"Anat. Anz."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)62907-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-5-5-543"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-6-2-117"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(61)90693-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.144.3626.1544"},{"key":"e_1_2_10_10_1","unstructured":"Medawar P.B.1963.Discussion after Miller J.F.A.P. and Osoba D. Role of the thymus in the origin of immunological competence. InThe Immunologically Competent Cell: Its Nature and Origin. Vol.16.G.E.W.Wostenholme&J.Knight Eds.:70.London:Ciba Foundation Study Group."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/199653a0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspl.1899.0121"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.10.4027"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90444-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/311385a0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1984.tb01113.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3616623"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90568-X"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/332040a0"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/333742a0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.4049\/jimmunol.108.3.586","article-title":"Suppressor T cells","volume":"108","author":"Gershon R.K.","year":"1972","journal-title":"J. Immunol."},{"key":"e_1_2_10_22_1","first-page":"1567","article-title":"Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt\u20101 effector cells for oocytes damage after adoptive transfer","volume":"156","author":"Sakaguchi S.","year":"1982","journal-title":"J. Exp. Med."},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.156.6.1577"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self\u2010tolerance maintained by activated T cells expressing IL\u20102 receptor alpha\u2010chain (CD25). Breakdown of a single mechanism of self\u2010tolerance causes various autoimmune diseases","volume":"155","author":"Sakaguchi S.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11679"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/83784"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0083-6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00236158"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3961493"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb35746.x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000124938"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.08.007"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000054324"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-4-8-1211"},{"key":"e_1_2_10_36_1","first-page":"115","article-title":"Evidence that insulin\u2010like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily","volume":"21","author":"Geenen V.","year":"1993","journal-title":"Thymus"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.1999.00343.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)10023-2"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.1998.00269.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90195-Q"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00304614"},{"key":"e_1_2_10_42_1","first-page":"55","article-title":"Membrane translocation and relationship with MHC class I of a human thymic neurophysin\u2010like molecule","volume":"22","author":"Geenen V.","year":"1993","journal-title":"Thymus"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(96)00105-X"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001241"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00052-0"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090000146"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni723"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031677"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00111-6"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115601"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082449"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707486105"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009265107"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02120"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1972.1"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7041259"},{"key":"e_1_2_10_57_1","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.4049\/jimmunol.142.10.3400","article-title":"Thymus transplantation and disease prevention in the diabetes\u2010prone Bio\u2010Breeding rat","volume":"142","author":"Georgiou H.M.","year":"1989","journal-title":"J. Immunol."},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.44.1.49"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4598"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni726"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.01.015"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90505-3"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.3.7360"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.182"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16584"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834450100"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.5.1383"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1448-y"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0476"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-289"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-293"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-399"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-393"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075958"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.08.006"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062497"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159407"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.005"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.013"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00195143"},{"key":"e_1_2_10_81_1","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.4049\/jimmunol.161.11.5918","article-title":"Transcription of a broad range of self\u2010antigens in human thymus suggesting a role for central mechanisms in tolerance towards peripheral antigens","volume":"161","author":"Sospedra M.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119032"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr247"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44583"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200493"},{"key":"e_1_2_10_86_1","first-page":"723","article-title":"The role a thymic tolerance in CNS autoimmune disease","volume":"14","author":"Handel A.E.","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075038"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09655"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3537"},{"key":"e_1_2_10_90_1","unstructured":"deBellis A. A.Bizzarro&A.Bellestella.2004.Autoimmune diabetes insipidus. InImmunoendocrinology in Health and Disease.V.Geenen&G.P.Chrousos Eds.:461\u2013490.New York NY:Marcel Dekker."},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.4651"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1360"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006103"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1707"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215488"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/85266"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2010.04.005"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1337.008"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00726-12"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.02.019"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.515262"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/251547a0"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.1"},{"key":"e_1_2_10_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-012-2077-7"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.14089","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nyas.14089","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.14089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T18:22:21Z","timestamp":1694197341000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/nyas.14089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,22]]},"references-count":103,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1111\/nyas.14089"],"URL":"https:\/\/doi.org\/10.1111\/nyas.14089","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"type":"print","value":"0077-8923"},{"type":"electronic","value":"1749-6632"}],"subject":[],"published":{"date-parts":[[2019,4,22]]},"assertion":[{"value":"2019-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}