{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:13:31Z","timestamp":1765728811597,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity. To further investigate this hypothesis, in our current study, we analyzed thymic expression of autoantigens, at the transcriptional and protein level, following in utero infection by CV-B4. mRNA expression levels of Igf2 and Myo7, major autoantigens of pancreas and heart, respectively, were analyzed in whole thymus and in enriched TECs together along with both transcription factors, Aire and Fezf2, involved in autoantigens expression in the thymus. Results show that in utero infection by CV-B4 induces a significant decrease in Igf2 and Myo7 expression at both mRNA and protein level in whole thymus and in enriched TECs as well. Moreover, a correlation between viral load and autoantigens expression can be observed in the whole thymus, indicating a direct effect of in utero infection by CV-B4 on autoantigens expression. Together, these results indicate that an in utero infection of the thymus by CV-B4 may interfere with self-tolerance establishment in TECs by decreasing autoantigen expression at both mRNA and protein level and thereby increase the risk of autoimmunity onset.<\/jats:p>","DOI":"10.3390\/microorganisms9071537","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T21:39:15Z","timestamp":1626730755000},"page":"1537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus"],"prefix":"10.3390","volume":"9","author":[{"given":"Aymen","family":"Halouani","sequence":"first","affiliation":[{"name":"Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives LR99ES27, Facult\u00e9 de Pharmacie de Monastir, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"},{"name":"Facult\u00e9 des Sciences de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1068, Tunisia"},{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Michaux","sequence":"additional","affiliation":[{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habib","family":"Jmii","sequence":"additional","affiliation":[{"name":"Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives LR99ES27, Facult\u00e9 de Pharmacie de Monastir, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"},{"name":"Facult\u00e9 des Sciences de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Trussart","sequence":"additional","affiliation":[{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahlem","family":"Chahbi","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9matologie, Facult\u00e9 de M\u00e9decine de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri","family":"Martens","sequence":"additional","affiliation":[{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Renard","sequence":"additional","affiliation":[{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahjoub","family":"Aouni","sequence":"additional","affiliation":[{"name":"Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives LR99ES27, Facult\u00e9 de Pharmacie de Monastir, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Hober","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie EA3610, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Lille, CHU Lille, 59000 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-7284","authenticated-orcid":false,"given":"Vincent","family":"Geenen","sequence":"additional","affiliation":[{"name":"GIGA-I3 Immunoendocrinologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Li\u00e8ge, CHU-B34, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-9405","authenticated-orcid":false,"given":"Hela","family":"Ja\u00efdane","sequence":"additional","affiliation":[{"name":"Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives LR99ES27, Facult\u00e9 de Pharmacie de Monastir, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/icb.1994.54","article-title":"Burnet oration. The thymus then and now","volume":"72","author":"Miller","year":"1994","journal-title":"Immunol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nri2993","article-title":"The golden anniversary of the thymus","volume":"11","author":"Miller","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1146\/annurev.immunol.17.1.829","article-title":"Selection of the T cell repertoire","volume":"17","author":"Sebzda","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nri1781","article-title":"Journey through the thymus, stromal guides for T-cell development and selection","volume":"6","author":"Takahama","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/0092-8674(89)90501-1","article-title":"Positive selection of the T cell repertoire, where and when does it occur?","volume":"58","author":"Benoist","year":"1989","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/102736620310001604910","article-title":"Thymic presentation of autoantigens and the efficiency of negative selection","volume":"5","year":"2003","journal-title":"Comput. Math. Methods Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.cell.2015.10.057","article-title":"Aire gets company for immune tolerance","volume":"163","author":"Klein","year":"2015","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/BOR.0b013e328353372d","article-title":"Update on coxsackievirus B3 myocarditis","volume":"24","author":"Fairweather","year":"2012","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/rmv.647","article-title":"Enteroviruses and type 1 diabetes, towards a better understanding of the relationship","volume":"20","author":"Sauter","year":"2010","journal-title":"Rev. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1196\/annals.1313.090","article-title":"Autoimmunity and coxsackievirus infection in primary Sj\u00f6gren\u2019s syndrome","volume":"1050","author":"Triantafyllopoulou","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tracy, S., and Gauntt, C. (2008). Group B coxsackievirus virulence. Group B Coxsackieviruses, Springer.","DOI":"10.1007\/978-3-540-75546-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/08916930500050277","article-title":"Infection, vaccines and other environmental triggers of autoimmunity","volume":"38","author":"Molina","year":"2005","journal-title":"Autoimmunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fimmu.2013.00321","article-title":"MHC class II polymorphisms, autoreactive T-cells, and autoimmunity","volume":"4","author":"Tsai","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fnins.2013.00187","article-title":"Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity","volume":"7","author":"Geenen","year":"2013","journal-title":"Front. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Savino, W. (2006). The thymus is a common target organ in infectious diseases. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020062"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.it.2013.06.004","article-title":"Tolerance has its limits, how the thymus copes with infection","volume":"34","author":"Nobrega","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-2249.2011.04558.x","article-title":"Immunology in the clinic review series, focus on type 1 diabetes and viruses, enterovirus, thymus and type 1 diabetes pathogenesis","volume":"168","author":"Hiar","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/dmrr.995","article-title":"Coxsackievirus B4 and type 1 diabetes pathogenesis: Contribution of animal models","volume":"25","author":"Gharbi","year":"2009","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1348-0421.2006.tb03874.x","article-title":"Prolonged viral RNA detection in blood and lymphoid tissues from coxsackievirus B4 E2 orally-inoculated Swiss mice","volume":"50","author":"Gharbi","year":"2006","journal-title":"Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJM195611082551902","article-title":"Acute aseptic myocarditis and meningoencephalitis in the newborn child infected with Coxsackie virus group B, type 3","volume":"255","author":"Kibrick","year":"1956","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1348-0421.2008.00002.x","article-title":"Infection of primary cultures of murine splenic and thymic cells with coxsackievirus B4","volume":"52","author":"Gharbi","year":"2008","journal-title":"Microbiol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1128\/JVI.76.10.5260-5265.2002","article-title":"Persistent infection of human thymic epithelial cells by coxsackievirus B4","volume":"76","author":"Brilot","year":"2002","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11151","DOI":"10.1128\/JVI.00726-12","article-title":"Persistent infection of thymic epithelial cells with coxsackievirus B4 results in decreased expression of type 2 insulin-like growth factor","volume":"86","author":"Caloone","year":"2012","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9854","DOI":"10.1128\/JVI.78.18.9854-9861.2004","article-title":"Coxsackievirus B4 infection of human fetal thymus cells","volume":"78","author":"Brilot","year":"2004","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/jmv.21016","article-title":"Coxsackievirus B4 infection of murine foetal thymus organ cultures","volume":"80","author":"Brilot","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/cei.12893","article-title":"In-utero coxsackievirus B4 infection of the mouse thymus","volume":"187","author":"Halouani","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_27","first-page":"741","article-title":"An immunofluorescent study of generalized Coxsackievirus B3 infection in a newborn infant","volume":"35","author":"Iwasaki","year":"1985","journal-title":"Pathol. Int."},{"key":"ref_28","first-page":"175","article-title":"Study of vertical transmission of coxsackie group enteroviruses in the etiology of congenital immunodeficiencies","volume":"42","author":"Lozovskaia","year":"1997","journal-title":"Vopr. Virusol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Halouani, A., Jmii, H., Michaux, H., Renard, C., Martens, H., Pirottin, D., Mastouri, M., Aouni, M., Geenen, V., and Ja\u00efdane, H. (2020). Housekeeping Gene Expression in the Fetal and Neonatal Murine Thymus Following Coxsackievirus B4 Infection. Genes, 11.","DOI":"10.3389\/fimmu.2020.00481"},{"key":"ref_31","first-page":"e50951","article-title":"Isolation of myeloid dendritic cells and epithelial cells from human thymus","volume":"79","author":"Stoeckle","year":"2013","journal-title":"JoVE"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dotti, I., and Bonin, S. (2011). DNase treatment of RNA. Guidelines for Molecular Analysis in Archive Tissues, Springer.","DOI":"10.1007\/978-3-642-17890-0_18"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1006\/mcpr.1994.1070","article-title":"Acute, chronic and persistent enterovirus and poliovirus infections, detection of viral genome by semi-nested PCR amplification in culture-negative samples","volume":"8","author":"Leparc","year":"1994","journal-title":"Mol. Cell. Probes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1128\/jcm.30.1.160-165.1992","article-title":"General primer-mediated polymerase chain reaction for detection of enteroviruses, application for diagnostic routine and persistent infections","volume":"30","author":"Zoll","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12985-017-0689-5","article-title":"Coxsackievirus B4 vertical transmission in a murine model","volume":"14","author":"Halouani","year":"2017","journal-title":"Virol. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Michaux, H., Halouani, A., Trussart, C., Renard, C., Ja\u00efdane, H., Martens, H., Geenen, V., and Hober, D. (2021). Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection. Microorganisms, 9.","DOI":"10.3390\/microorganisms9020402"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1126\/science.275.5304.1320","article-title":"Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5","volume":"275","author":"Bergelson","year":"1997","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1146\/annurev.immunol.23.021704.115601","article-title":"A central role for central tolerance","volume":"24","author":"Kyewski","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000328844","article-title":"Expression of the growth hormone\/insulin-like growth factor axis during Balb\/c thymus ontogeny and effects of growth hormone upon ex vivo T cell differentiation","volume":"19","author":"Kermani","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1126\/science.aaa7017","article-title":"Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance","volume":"348","author":"Yang","year":"2015","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","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":"ref_44","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.cell.2015.10.013","article-title":"Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance","volume":"163","author":"Takaba","year":"2015","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","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":"ref_46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrendo.2010.200","article-title":"The role of AIRE in human autoimmune disease","volume":"7","author":"Akirav","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature10945","article-title":"De novo mutations revealed by whole-exome sequencing are strongly associated with autism","volume":"485","author":"Sanders","year":"2012","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/B978-0-12-418700-9.00006-X","article-title":"Transcriptional dysregulation of neocortical circuit assembly in ASD","volume":"113","author":"Kwan","year":"2013","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1093\/carcin\/bgt165","article-title":"FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma","volume":"34","author":"Shu","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_50","first-page":"115","article-title":"Evidence that insulin-like growth factor 2 (IGF2), is the dominant thymic peptide of the insulin superfamily","volume":"21","author":"Geenen","year":"1993","journal-title":"Thymus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/dmrr.182","article-title":"Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes","volume":"17","author":"Achour","year":"2001","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3389\/fimmu.2015.00338","article-title":"How does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 diabetes?","volume":"6","author":"Michaux","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1172\/JCI44583","article-title":"Impaired thymic tolerance to \u03b1-myosin directs autoimmunity to the heart in mice and humans","volume":"121","author":"Lv","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1084\/jem.20031677","article-title":"Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters","volume":"199","author":"Gotter","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/ni723","article-title":"Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self","volume":"2","author":"Derbinski","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/01.RES.87.4.328","article-title":"Host gene regulation during coxsackievirus B3 infection in mice, assessment by microarrays","volume":"87","author":"Taylor","year":"2000","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1007\/s00125-005-1839-7","article-title":"Global profiling of coxsackievirus-and cytokine-induced gene expression in human pancreatic islets","volume":"48","author":"Ylipaasto","year":"2005","journal-title":"Diabetologia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/j.jprot.2011.05.022","article-title":"Comparative proteome analyses of host protein expression in response to Enterovirus 71 and Coxsackievirus A16 infections","volume":"74","author":"Lee","year":"2011","journal-title":"J. Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/cimm.1995.1037","article-title":"Deficient antigen presentation by thymic epithelial cells reveals differential induction of T cell clone effector functions by CD28-mediated costimulation","volume":"161","author":"Lepesant","year":"1995","journal-title":"Cell. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3389\/fimmu.2015.00093","article-title":"Promiscuous gene expression in the thymus, a matter of epigenetics, miRNA, and more?","volume":"6","author":"Ucar","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","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":"ref_62","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41590-020-0717-2","article-title":"Chd4 choreographs self-antigen expression for central immune tolerance","volume":"21","author":"Tomofuji","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fimmu.2013.00249","article-title":"Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases","volume":"4","author":"Akiyama","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.it.2017.07.010","article-title":"The mechanisms of T cell selection in the thymus","volume":"38","author":"Takaba","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Tedford, E., and McConkey, G. (2017). Neurophysiological changes induced by chronic Toxoplasma gondii infection. Pathogens, 6.","DOI":"10.20944\/preprints201705.0071.v1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.immuni.2005.09.016","article-title":"Human TLR-7-,-8-, and-9-mediated induction of IFN-\u03b1\/\u03b2 and-\u03bb is IRAK-4 dependent and redundant for protective immunity to viruses","volume":"23","author":"Yang","year":"2005","journal-title":"Immunity"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15623","DOI":"10.1073\/pnas.95.26.15623","article-title":"Identification of genes differentially regulated by interferon \u03b1, \u03b2, or \u03b3 using oligonucleotide arrays","volume":"95","author":"Der","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E559","DOI":"10.1152\/ajpendo.90770.2008","article-title":"Effects of type I interferons on IGF-mediated autocrine\/paracrine growth of human neuroendocrine tumor cells","volume":"296","author":"Vitale","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1530\/ERC-12-0217","article-title":"Interferon-beta is a potent inhibitor of cell growth and cortisol production In Vitro and sensitizes human adrenocortical carcinoma cells to mitotane","volume":"20","author":"Vitale","year":"2013","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/ni.3731","article-title":"The multiple pathways to autoimmunity","volume":"18","author":"Theofilopoulos","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Cui, L., Qi, Y., Li, H., Ge, Y., Zhao, K., Qi, X., Guo, X., Shi, Z., Zhou, M., and Zhu, B. (2011). Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027071"},{"key":"ref_72","first-page":"615","article-title":"The Role of Aire, microRNAs and Cell\u2013Cell Interactions on Thymic Architecture and Induction of Tolerance","volume":"6","author":"Passos","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fimmu.2020.00481","article-title":"Assessment of Thymic Output Dynamics After in utero Infection of Mice with Coxsackievirus B4","volume":"11","author":"Halouani","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:31:58Z","timestamp":1760164318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":73,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["microorganisms9071537"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9071537","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2021,7,19]]}}}