{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:09:06Z","timestamp":1785431346571,"version":"3.56.0"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"7","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2014-2020. 4.01.15-0012"],"award-info":[{"award-number":["2014-2020. 4.01.15-0012"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Joint Program on Rare Diseases","award":["EJP RD JTC 2019"],"award-info":[{"award-number":["EJP RD JTC 2019"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-19-RAR4-0011-4"],"award-info":[{"award-number":["ANR-19-RAR4-0011-4"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG377"],"award-info":[{"award-number":["PRG377"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG1117"],"award-info":[{"award-number":["PRG1117"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG2011"],"award-info":[{"award-number":["PRG2011"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Excellence for Genomics and Translational Medicine"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,7]]},"abstract":"<jats:p>Recent studies have highlighted the role of the thymus in maintaining immune tolerance to type 1 interferons (T1 IFNs). Individuals with thymic abnormalities, such as autoimmune regulator (AIRE) gene mutations, frequently develop neutralizing autoantibodies to interferon-alpha (IFN\u03b1). Unlike mice, Aire-deficient rats develop robust autoantibodies to IFN\u03b1. Using this rat model, we show that Aire regulates the thymic expression of interferon-stimulated genes (ISGs), which occurs before developing anti-IFN\u03b1 autoantibodies. In the periphery, we observed a widespread downregulation of ISGs across immune cells and reduced activation of natural killer (NK) cells. Furthermore, the presence of anti-IFN\u03b1 autoantibodies correlated with reduced peripheral tissue inflammation, suggesting their role in dampening T1 IFN signaling and minimizing tissue infiltration. Our findings reveal that Aire-mediated regulation of thymic T1 IFN signaling is linked to the production of protective anti-IFN\u03b1 autoantibodies, which inversely correlate with autoimmune pathology in peripheral tissues.<\/jats:p>","DOI":"10.1084\/jem.20241403","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T02:21:11Z","timestamp":1743128471000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Impaired Aire-dependent IFN signaling in the thymus precedes the protective autoantibodies to IFN\u03b1"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3028-2977","authenticated-orcid":true,"given":"Artur","family":"Stoljar","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-315X","authenticated-orcid":true,"given":"Maksym","family":"Zarodniuk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6144-6504","authenticated-orcid":true,"given":"Rudolf","family":"Bichele","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1379-1183","authenticated-orcid":true,"given":"Elise Helene","family":"Armulik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-6020","authenticated-orcid":true,"given":"Uku","family":"Haljasorg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2995-5161","authenticated-orcid":true,"given":"Romain","family":"Humeau","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gnr7b55","id-type":"ROR","asserted-by":"publisher"}],"name":"Nantes University, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CNRS 3 , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-5528","authenticated-orcid":true,"given":"Marine","family":"Besnard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gnr7b55","id-type":"ROR","asserted-by":"publisher"}],"name":"Nantes University, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CNRS 3 , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-9808","authenticated-orcid":true,"given":"Liis","family":"Haljasm\u00e4gi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7533-9248","authenticated-orcid":true,"given":"Liina","family":"Tserel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9497-4470","authenticated-orcid":true,"given":"Merili","family":"Peltser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-3715","authenticated-orcid":true,"given":"Ahto","family":"Salumets","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-108X","authenticated-orcid":true,"given":"Eliisa","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040af2s02","id-type":"ROR","asserted-by":"publisher"}],"name":"Translational Immunology Research Program, Faculty of Medicine, University of Helsinki 2 , Helsinki,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-4648","authenticated-orcid":true,"given":"Kai","family":"Kisand","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7195-0631","authenticated-orcid":true,"given":"Carole","family":"Guillonneau","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gnr7b55","id-type":"ROR","asserted-by":"publisher"}],"name":"Nantes University, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CNRS 3 , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0448-8627","authenticated-orcid":true,"given":"Martti","family":"Laan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6755-791X","authenticated-orcid":true,"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03z77qz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedicine and Translational Medicine, University of Tartu 1 , Tartu,","place":["Estonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025043022052637500_bib1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.immuni.2005.07.005","article-title":"The cellular mechanism of Aire control of T cell tolerance","volume":"23","author":"Anderson","year":"2005","journal-title":"Immunity"},{"key":"2025043022052637500_bib2","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1126\/science.1075958","article-title":"Projection of an immunological self shadow within the thymus by the aire protein","volume":"298","author":"Anderson","year":"2002","journal-title":"Science"},{"key":"2025043022052637500_bib3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adp1139","article-title":"Sterile production of interferons in the thymus affects T cell repertoire selection","volume":"9","author":"Ashby","year":"2024","journal-title":"Sci. Immunol."},{"key":"2025043022052637500_bib4","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4340","article-title":"Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths","volume":"6","author":"Bastard","year":"2021","journal-title":"Sci. Immunol."},{"key":"2025043022052637500_bib5","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.4049\/jimmunol.2000225","article-title":"IFN-\u03bb enhances constitutive expression of MHC class I molecules on thymic epithelial cells","volume":"205","author":"Benhammadi","year":"2020","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI156507","article-title":"Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome","volume":"132","author":"Besnard","year":"2022","journal-title":"J. Clin. Invest."},{"key":"2025043022052637500_bib7","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41586-018-0346-1","article-title":"Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells","volume":"559","author":"Bornstein","year":"2018","journal-title":"Nature"},{"key":"2025043022052637500_bib8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41577-023-00933-2","article-title":"Anti-cytokine autoantibodies: Mechanistic insights and disease associations","volume":"24","author":"Cheng","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"2025043022052637500_bib9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024252","article-title":"IFN-\u03b1 is constitutively expressed in the human thymus, but not in peripheral lymphoid organs","volume":"6","author":"Colantonio","year":"2011","journal-title":"PLoS One"},{"key":"2025043022052637500_bib10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41587-021-01033-z","article-title":"Differential abundance testing on single-cell data using k-nearest neighbor graphs","volume":"40","author":"Dann","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"2025043022052637500_bib11","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":"2025043022052637500_bib12","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.2337\/db13-1777","article-title":"A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes","volume":"63","author":"Ferreira","year":"2014","journal-title":"Diabetes"},{"key":"2025043022052637500_bib13","doi-asserted-by":"publisher","first-page":"976","DOI":"10.3389\/fimmu.2017.00976","article-title":"Autoantibody repertoire in APECED patients targets two distinct subgroups of proteins","volume":"8","author":"Fishman","year":"2017","journal-title":"Front. Immunol."},{"key":"2025043022052637500_bib55","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s13059-020-02136-7","article-title":"pipeComp, a general framework for the evaluation of computational pipelines, reveals performant single cell RNA-seq preprocessing tools.","volume":"21","author":"Germain","year":"2020","journal-title":"Genome Biol."},{"key":"2025043022052637500_bib14","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1073\/pnas.1119351109","article-title":"Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells","volume":"109","author":"Giraud","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025043022052637500_bib15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nri3133","article-title":"Immunomodulatory functions of type I interferons","volume":"12","author":"Gonz\u00e1lez-Navajas","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"2025043022052637500_bib16","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.immuni.2012.01.011","article-title":"Constitutive type I interferon modulates homeostatic balance through tonic signaling","volume":"36","author":"Gough","year":"2012","journal-title":"Immunity"},{"key":"2025043022052637500_bib17","doi-asserted-by":"publisher","first-page":"7269","DOI":"10.4049\/jimmunol.173.12.7269","article-title":"Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection","volume":"173","author":"Gurney","year":"2004","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib56","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression.","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol."},{"key":"2025043022052637500_bib18","doi-asserted-by":"publisher","first-page":"3246","DOI":"10.1002\/eji.201545928","article-title":"A highly conserved NF-\u03baB-responsive enhancer is critical for thymic expression of Aire in mice","volume":"45","author":"Haljasorg","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"2025043022052637500_bib19","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1084\/jem.20190993","article-title":"IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus","volume":"216","author":"Hemmers","year":"2019","journal-title":"J. Exp. Med."},{"key":"2025043022052637500_bib20","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abe3454","article-title":"Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells","volume":"6","author":"Hetem\u00e4ki","year":"2021","journal-title":"Sci. Immunol."},{"key":"2025043022052637500_bib21","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.4049\/jimmunol.0802124","article-title":"Aire-deficient C57BL\/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype","volume":"182","author":"Hubert","year":"2009","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2025043022052637500_bib23","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.2337\/db13-1775","article-title":"Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility","volume":"63","author":"Kallionp\u00e4\u00e4","year":"2014","journal-title":"Diabetes"},{"key":"2025043022052637500_bib24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1084\/jem.20091669","article-title":"Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines","volume":"207","author":"Kisand","year":"2010","journal-title":"J. Exp. Med."},{"key":"2025043022052637500_bib25","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1182\/blood-2008-03-144634","article-title":"Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes","volume":"112","author":"Kisand","year":"2008","journal-title":"Blood"},{"key":"2025043022052637500_bib26","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s10875-015-0176-y","article-title":"Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy","volume":"35","author":"Kisand","year":"2015","journal-title":"J. Clin. Immunol."},{"key":"2025043022052637500_bib27","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.molimm.2007.05.014","article-title":"Modulation of Aire regulates the expression of tissue-restricted antigens","volume":"45","author":"Kont","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025043022052637500_bib28","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.4049\/jimmunol.174.4.1862","article-title":"Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice","volume":"174","author":"Kuroda","year":"2005","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib29","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/s41586-023-06717-x","article-title":"Autoantibodies against type I IFNs in humans with alternative NF-\u03baB pathway deficiency","volume":"623","author":"Le Voyer","year":"2023","journal-title":"Nature"},{"key":"2025043022052637500_bib30","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.4049\/jimmunol.0804277","article-title":"Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo","volume":"183","author":"Lienenklaus","year":"2009","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib31","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1084\/jem.20040581","article-title":"Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity","volume":"200","author":"Liston","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025043022052637500_bib32","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/ni906","article-title":"Aire regulates negative selection of organ-specific T cells","volume":"4","author":"Liston","year":"2003","journal-title":"Nat. Immunol."},{"key":"2025043022052637500_bib33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2200413119","article-title":"The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies","volume":"119","author":"Manry","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025043022052637500_bib34","doi-asserted-by":"publisher","first-page":"102389","DOI":"10.1016\/j.coi.2023.102389","article-title":"The role of interferon in the thymus","volume":"84","author":"Martinez","year":"2023","journal-title":"Curr. Opin. Immunol."},{"key":"2025043022052637500_bib35","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1146\/annurev.immunol.25.022106.141532","article-title":"Aire","volume":"27","author":"Mathis","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"2025043022052637500_bib36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030289","article-title":"Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1","volume":"3","author":"Meager","year":"2006","journal-title":"PLoS Med."},{"key":"2025043022052637500_bib37","doi-asserted-by":"publisher","first-page":"4265","DOI":"10.4049\/jimmunol.1500036","article-title":"IFN-\u03b1\/\u03b2 receptor signaling promotes regulatory T cell development and function under stress conditions","volume":"194","author":"Metidji","year":"2015","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib38","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.cell.2016.06.024","article-title":"AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies","volume":"166","author":"Meyer","year":"2016","journal-title":"Cell"},{"key":"2025043022052637500_bib39","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1016\/j.cell.2022.05.018","article-title":"Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells","volume":"185","author":"Michelson","year":"2022","journal-title":"Cell"},{"key":"2025043022052637500_bib40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024972","article-title":"T cell-intrinsic and -extrinsic contributions of the IFNAR\/STAT1-axis to thymocyte survival","volume":"6","author":"Moro","year":"2011","journal-title":"PLoS One"},{"key":"2025043022052637500_bib41","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2015.12.032","article-title":"Parsing the interferon transcriptional network and its disease associations","volume":"164","author":"Mostafavi","year":"2016","journal-title":"Cell"},{"key":"2025043022052637500_bib60","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jaut.2015.07.002","article-title":"Type I and II interferon signatures in Sjogren\u2019s syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren\u2019s related lymphomagenesis.","volume":"63","author":"Nezos","year":"2015","journal-title":"J. Autoimmun."},{"key":"2025043022052637500_bib42","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1172\/JCI26971","article-title":"Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice","volume":"116","author":"Niki","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025043022052637500_bib43","doi-asserted-by":"publisher","first-page":"1327784","DOI":"10.3389\/fimmu.2024.1327784","article-title":"Interferon autoantibodies as signals of a sick thymus","volume":"15","author":"Oftedal","year":"2024","journal-title":"Front. Immunol."},{"key":"2025043022052637500_bib44","doi-asserted-by":"publisher","first-page":"874","DOI":"10.4049\/jimmunol.1701318","article-title":"Breakdown of immune tolerance in AIRE-deficient rats induces a severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy-like autoimmune disease","volume":"201","author":"Ossart","year":"2018","journal-title":"J. Immunol."},{"key":"2025043022052637500_bib45","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1038\/nri2450","article-title":"Transcriptional regulation by AIRE: Molecular mechanisms of central tolerance","volume":"8","author":"Peterson","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025043022052637500_bib46","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1016\/j.devcel.2023.08.017","article-title":"Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus","volume":"58","author":"Ragazzini","year":"2023","journal-title":"Dev. Cell"},{"key":"2025043022052637500_bib47","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/eji.1830160410","article-title":"Antigen presentation by human monocytes: Effects of modifying major histocompatibility complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids","volume":"16","author":"Rhodes","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"2025043022052637500_bib53","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1084\/jem.20161451","article-title":"Detection of interferon alpha protein reveals differential levels and cellular sources in disease.","volume":"214","author":"Rodero","year":"2017","journal-title":"J. Exp. Med."},{"key":"2025043022052637500_bib59","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1101\/gr.171645.113","article-title":"Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.","volume":"24","author":"Sansom","year":"2014","journal-title":"Genome Res."},{"key":"2025043022052637500_bib57","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data.","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2025043022052637500_bib48","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nri3044","article-title":"NK cell development, homeostasis and function: Parallels with CD8+ T cells","volume":"11","author":"Sun","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025043022052637500_bib49","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev.immunol.23.021704.115843","article-title":"Type I interferons (alpha\/beta) in immunity and autoimmunity","volume":"23","author":"Theofilopoulos","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2025043022052637500_bib58","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1038\/s41467-020-14766-3","article-title":"Trajectory-based differential expression analysis for single-cell sequencing data.","volume":"11","author":"Van den Berge","year":"2020","journal-title":"Nat. Commun."},{"key":"2025043022052637500_bib50","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1093\/intimm\/dxy073","article-title":"Hassall\u2019s corpuscles with cellular-senescence features maintain IFN\u03b1 production through neutrophils and pDC activation in the thymus","volume":"31","author":"Wang","year":"2019","journal-title":"Int. Immunol."},{"key":"2025043022052637500_bib51","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1210\/jc.2006-1873","article-title":"Autoimmune polyendocrine syndrome type 1 in Norway: Phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene","volume":"92","author":"Wolff","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2025043022052637500_bib54","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","article-title":"Scrublet: Computational identification of cell doublets in sngle-cell transcriptomic data.","volume":"8","author":"Wolock","year":"2019","journal-title":"Cell Syst."},{"key":"2025043022052637500_bib52","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/ni.3419","article-title":"Late stages of T cell maturation in the thymus involve NF-\u03baB and tonic type I interferon signaling","volume":"17","author":"Xing","year":"2016","journal-title":"Nat. Immunol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241403\/1943788\/jem_20241403.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241403\/1943788\/jem_20241403.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T22:05:34Z","timestamp":1746050734000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/222\/7\/e20241403\/277668\/Impaired-Aire-dependent-IFN-signaling-in-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":60,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20241403","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"article-number":"e20241403"}}