{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:53:44Z","timestamp":1793969624463,"version":"4.8.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.00447","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T04:26:36Z","timestamp":1552623996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":89,"title":["Thymic Epithelium Abnormalities in DiGeorge and Down Syndrome Patients Contribute to Dysregulation in T Cell Development"],"prefix":"10.3389","volume":"10","author":[{"given":"Genni Enza","family":"Marcovecchio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Bortolomai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferrua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Imberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Conforti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Amodio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Bergante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Macchiarulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"D'Oria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Cesare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Fousteri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Carotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giamberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro Luigi","family":"Poliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Cancrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Villa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marita","family":"Bosticardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/j.0105-2896.2006.00348.x","article-title":"Central tolerance: good but imperfect","volume":"209","author":"Gallegos","year":"2006","journal-title":"Immunol Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1084\/jem.20050471","article-title":"Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels","volume":"202","author":"Derbinski","year":"2005","journal-title":"J Exp Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/BF00278938","article-title":"A deletion in chromosome 22 can cause DiGeorge syndrome","volume":"57","author":"de la Chapelle","year":"1981","journal-title":"Hum Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0022-3476(82)80116-9","article-title":"The association of the DiGeorge anomalad with partial monosomy of chromosome 22","volume":"101","author":"Kelley","year":"1982","journal-title":"J Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fimmu.2013.00322","article-title":"Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia","volume":"4","author":"Davies","year":"2013","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3727\/000000006781510697","article-title":"When half is not enough: gene expression and dosage in the 22q11 deletion syndrome","volume":"13","author":"Meechan","year":"2007","journal-title":"Gene Expr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1093\/hmg\/8.7.1157","article-title":"A common molecular basis for rearrangement disorders on chromosome 22q11","volume":"8","author":"Edelmann","year":"1999","journal-title":"Hum Mol Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1136\/jmg.32.9.746","article-title":"Monozygotic twins with chromosome 22q11 deletion and discordant phenotype","volume":"32","author":"Goodship","year":"1995","journal-title":"J Med Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1002\/ajmg.a.38597","article-title":"Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome","volume":"176","author":"Crowley","year":"2017","journal-title":"Am J Med Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1006\/dbio.2001.0283","article-title":"Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development","volume":"235","author":"Garg","year":"2001","journal-title":"Dev Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1086\/511993","article-title":"Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions","volume":"80","author":"Zweier","year":"2007","journal-title":"Am J Hum Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.jpeds.2013.12.013","article-title":"Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome","volume":"164","author":"Ferrando-Mart\u00ednez","year":"2014","journal-title":"J Pediatr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.jpeds.2014.01.056","article-title":"Clinical features and follow-up in patients with 22q11.2 deletion syndrome","volume":"164","author":"Cancrini","year":"2014","journal-title":"J Pediatr"},{"key":"B14","doi-asserted-by":"publisher","first-page":"F1000","DOI":"10.12688\/f1000research.7506.1","article-title":"The importance of understanding individual differences in Down syndrome","volume":"5","author":"Karmiloff-Smith","year":"2016","journal-title":"F1000Research"},{"key":"B15","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/ajmg.1320370745","article-title":"Morphological and immunohistochemical study of Down syndrome thymus","volume":"7","author":"Larocca","year":"1990","journal-title":"Am J Med Genet Suppl"},{"key":"B16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1365-2249.2009.03890.x","article-title":"Intrinsic defect of the immune system in children with down syndrome: a review","volume":"156","author":"Kusters","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/imm.12092","article-title":"Defective thymic progenitor development and mature T-cell responses in a mouse model for down syndrome","volume":"139","author":"Lorenzo","year":"2013","journal-title":"Immunology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/pai.12420","article-title":"Autoimmunity and regulatory T cells in 22q11.2 deletion syndrome patients","volume":"26","author":"Di Cesare","year":"2015","journal-title":"Pediatr Allergy Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4500","DOI":"10.4049\/jimmunol.1001700","article-title":"Decreased thymic output accounts for decreased naive T cell numbers in children with down syndrome","volume":"186","author":"Bloemers","year":"2011","journal-title":"J Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1182\/blood-2003-08-2824","article-title":"T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome","volume":"103","author":"Piliero","year":"2014","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/acel.12326","article-title":"How sex and age affect immune responses, susceptibility to infections, and response to vaccination","volume":"14","author":"Giefing-Kr\u00f6ll","year":"2015","journal-title":"Aging Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/ajt.13456","article-title":"Discarded human thymus is a novel source of stable and long-lived therapeutic regulatory T Cells","volume":"16","author":"Dijke","year":"2016","journal-title":"Am J Transplant"},{"key":"B23","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.clim.2010.04.005","article-title":"Simultaneous quantification of recent thymic T-cell and bone marrow B-cell emigrants in patients with primary immunodeficiency undergone to stem cell transplantation","volume":"136","author":"Sottini","year":"2010","journal-title":"Clin Immunol"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1002\/9780470689516","volume-title":"Permutation Tests for Complex Data: Theory, Applications and Software","author":"Pesarin","year":"2010"},{"key":"B25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/j.1474-9726.2007.00365.x","article-title":"Architectural changes in the thymus of aging mice","volume":"7","author":"Aw","year":"2007","journal-title":"Aging Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3389\/fimmu.2012.00019","article-title":"Post-AIRE maturation of thymic epithelial cells involves selective expression of keratinocyte-specific autoantigens","volume":"3","author":"Wang","year":"2012","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.4049\/jimmunol.155.4.1862","article-title":"Characterization of distinct stages during the differentiation of human CD69+CD3+ thymocytes and identification of thymic emigrants","volume":"155","author":"Vanhecke","year":"1995","journal-title":"J Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1002\/stem.1145","article-title":"Human T-lymphoid progenitors generated in a feeder-cell-free delta-like-4 culture system promote T-cell reconstitution in NOD\/SCID\/\u03b3c\u2212\/\u2212 mice","volume":"30","author":"Reimann","year":"2012","journal-title":"Stem Cells"},{"key":"B29","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fimmu.2016.00276","article-title":"Helios should not be cited as a marker of human thymus-derived Tregs. Commentary: Helios+ and Helios\u2212 cells coexist within the natural FoxP3+ T regulatory cell subset in humans","volume":"7","author":"Elkord","year":"2016","journal-title":"Front Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"976","DOI":"10.4049\/jimmunol.1102964","article-title":"Expression of Helios in peripherally induced FoxP3+ regulatory cells","volume":"188","author":"Gottschalk","year":"2012","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"144","DOI":"10.4049\/jimmunol.1501704","article-title":"Helios controls a limited subset of regulatory T cell functions","volume":"196","author":"Sebastian","year":"2016","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1146\/annurev-immunol-032712-100010","article-title":"The biology of recent thymic emigrants","volume":"31","author":"Fink","year":"2013","journal-title":"Annu Rev Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3389\/fimmu.2018.00098","article-title":"Twenty years of AIRE","volume":"9","author":"Perniola","year":"2018","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nri.2016.9","article-title":"AIRE expands: new roles in immune tolerance and beyond","volume":"16","author":"Su","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3389\/fimmu.2015.00081","article-title":"Thymic stromal alterations and genetic disorders of immune system","volume":"6","author":"Pignata","year":"2015","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fimmu.2011.00015","article-title":"Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency","volume":"2","author":"Rucci","year":"2011","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1365-2249.2010.04152.x","article-title":"Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles","volume":"161","author":"Lima","year":"2010","journal-title":"Clin Exp Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jaut.2010.07.008","article-title":"Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population","volume":"35","author":"Laakso","year":"2010","journal-title":"J Autoimmun"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1742-4933-2-4","article-title":"Direct analysis of thymic function in children with Down's syndrome","volume":"16","author":"Prada","year":"2005","journal-title":"Immun Ageing"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.4049\/jimmunol.1003053","article-title":"Decreased AIRE expression and global thymic hypofunction in down syndrome","volume":"187","author":"Lima","year":"2011","journal-title":"J Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.4049\/jimmunol.1400742","article-title":"Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype","volume":"193","author":"Skogberg","year":"2014","journal-title":"J Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1089\/ars.2010.3798","article-title":"Defective hematopoietic stem cell and lymphoid progenitor development in the Ts65Dn mouse model of down syndrome: potential role of oxidative stress","volume":"15","author":"Lorenzo","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"B43","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1089\/rej.2007.0648","article-title":"Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with down syndrome","volume":"11","author":"Roat","year":"2008","journal-title":"Rejuvenation Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1111\/j.1365-2249.2012.04610.x","article-title":"Down syndrome, autoimmunity and T regulatory cells","volume":"169","author":"Pellegrini","year":"2012","journal-title":"Clin Exp Immunol."},{"key":"B45","first-page":"538","article-title":"Down syndrome: is it really characterized by precocious immunosenescence?","volume":"2","author":"Kusters","year":"2011","journal-title":"Aging Dis."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00447\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T14:35:32Z","timestamp":1694702132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00447\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,15]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2019.00447"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.00447","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,15]]},"article-number":"447"}}