A. C. Monteleone-Cassiano, R. D. Pinto, P. Ferreirinha, U. G. Cipriano, A. F. Gembre, V. L. D. Bonato, G. A. Passos, N. L. Alves, E. A. Donadi
The autoimmune regulator (AIRE) gene deficiency in humans causes the autoimmune polyglandular syndrome type 1 (APS-1). AIRE contributes to self-tolerance and prevents autoimmunity via the regulation of tissue-restricted antigen (TRA) expression in medullary thymic epithelial cells (mTECs). Using a murine Aire-deficient mTEC line (Aire−/−), we previously reported that Aire regulates cell adhesion genes, affecting homotypic mTEC/mTEC and heterotypic mTEC/thymocyte interaction in vitro. Transcriptional analysis comparing AireWT with Aire−/− mTECs indicates that Aire modulates antigen processing and presentation genes. Aire−/− mTECs, but not AireWT, exhibited delayed expression of MHC II and CD74 molecules, suggesting that Aire influences the MHC II presentation pathway. However, AireWT and Aire−/− mTECs did not directly present the OVA323–339 peptide to OT-II TCR transgenic single-positive CD4+ T cells. When cocultured with splenocytes and dendritic cells, both mTEC types induce T cell activation and present the OVA323–339 peptide to OT-II TCR transgenic T cells. To further understand Aire's role in MHC II antigen processing/presentation, we evaluated the expression of the MHC II transactivator (Ciita), IFN-γ receptors and IFN-γ-induced GTPases, as well as lysosome and cathepsin L activities. After IFN-γ treatment, Aire−/− mTECs, but not AireWT, delayed the expression of Ciita. Our results suggest that Aire controls some steps of the MHC II antigen processing/presentation-related proteins.
{"title":"The Role of the Autoimmune Regulator Gene in the Control of MHC II Antigen-Processing and Presentation by Medullary Thymic Epithelial Cells","authors":"A. C. Monteleone-Cassiano, R. D. Pinto, P. Ferreirinha, U. G. Cipriano, A. F. Gembre, V. L. D. Bonato, G. A. Passos, N. L. Alves, E. A. Donadi","doi":"10.1111/tan.70516","DOIUrl":"10.1111/tan.70516","url":null,"abstract":"<p>The autoimmune regulator (<i>AIRE</i>) gene deficiency in humans causes the autoimmune polyglandular syndrome type 1 (APS-1). <i>AIRE</i> contributes to self-tolerance and prevents autoimmunity via the regulation of tissue-restricted antigen (TRA) expression in medullary thymic epithelial cells (mTECs). Using a murine <i>Aire</i>-deficient mTEC line (<i>Aire</i><sup>−/−</sup>), we previously reported that <i>Aire</i> regulates cell adhesion genes, affecting homotypic mTEC/mTEC and heterotypic mTEC/thymocyte interaction in vitro. Transcriptional analysis comparing <i>Aire</i><sup><i>WT</i></sup> with <i>Aire</i><sup><i>−/−</i></sup> mTECs indicates that <i>Aire</i> modulates antigen processing and presentation genes. <i>Aire</i><sup>−/−</sup> mTECs, but not <i>Aire</i><sup><i>WT</i></sup>, exhibited delayed expression of MHC II and CD74 molecules, suggesting that <i>Aire</i> influences the MHC II presentation pathway. However, <i>Aire</i><sup><i>WT</i></sup> and <i>Aire</i><sup>−/−</sup> mTECs did not directly present the OVA<sup>323–339</sup> peptide to OT-II TCR transgenic single-positive CD4+ T cells. When cocultured with splenocytes and dendritic cells, both mTEC types induce T cell activation and present the OVA<sup>323–339</sup> peptide to OT-II TCR transgenic T cells. To further understand <i>Aire'</i>s role in MHC II antigen processing/presentation, we evaluated the expression of the MHC II transactivator (<i>Ciita</i>), IFN-γ receptors and IFN-γ-induced GTPases, as well as lysosome and cathepsin L activities. After IFN-γ treatment, <i>Aire</i><sup>−/−</sup> mTECs, but not <i>Aire</i><sup><i>WT</i></sup>, delayed the expression of <i>Ciita</i>. Our results suggest <i>that Aire</i> controls some steps of the MHC II antigen processing/presentation-related proteins.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"106 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}