Models of Aire-dependent gene regulation for thymic negative selection
Mutations in the Autoimmune Regulator (AIRE) gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular l...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2011-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00014/full |
| _version_ | 1818131187775832064 |
|---|---|
| author | Dina eDanso-Abeam Dina eDanso-Abeam Stephanie eHumblet-Baron Stephanie eHumblet-Baron James eDooley James eDooley Adrian eListon Adrian eListon |
| author_facet | Dina eDanso-Abeam Dina eDanso-Abeam Stephanie eHumblet-Baron Stephanie eHumblet-Baron James eDooley James eDooley Adrian eListon Adrian eListon |
| author_sort | Dina eDanso-Abeam |
| collection | DOAJ |
| description | Mutations in the Autoimmune Regulator (AIRE) gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs) in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses. |
| first_indexed | 2024-12-11T08:16:57Z |
| format | Article |
| id | doaj.art-1419222dbf5f4ca097524ec8744b4da9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T08:16:57Z |
| publishDate | 2011-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1419222dbf5f4ca097524ec8744b4da92022-12-22T01:14:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-05-01210.3389/fimmu.2011.0001410901Models of Aire-dependent gene regulation for thymic negative selectionDina eDanso-Abeam0Dina eDanso-Abeam1Stephanie eHumblet-Baron2Stephanie eHumblet-Baron3James eDooley4James eDooley5Adrian eListon6Adrian eListon7VIBUniversity of LeuvenVIBUniversity of LeuvenVIBUniversity of LeuvenVIBUniversity of LeuvenMutations in the Autoimmune Regulator (AIRE) gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs) in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00014/fullAutoimmunitytolerancetranscription factorAIREtissue restricted antigen |
| spellingShingle | Dina eDanso-Abeam Dina eDanso-Abeam Stephanie eHumblet-Baron Stephanie eHumblet-Baron James eDooley James eDooley Adrian eListon Adrian eListon Models of Aire-dependent gene regulation for thymic negative selection Frontiers in Immunology Autoimmunity tolerance transcription factor AIRE tissue restricted antigen |
| title | Models of Aire-dependent gene regulation for thymic negative selection |
| title_full | Models of Aire-dependent gene regulation for thymic negative selection |
| title_fullStr | Models of Aire-dependent gene regulation for thymic negative selection |
| title_full_unstemmed | Models of Aire-dependent gene regulation for thymic negative selection |
| title_short | Models of Aire-dependent gene regulation for thymic negative selection |
| title_sort | models of aire dependent gene regulation for thymic negative selection |
| topic | Autoimmunity tolerance transcription factor AIRE tissue restricted antigen |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00014/full |
| work_keys_str_mv | AT dinaedansoabeam modelsofairedependentgeneregulationforthymicnegativeselection AT dinaedansoabeam modelsofairedependentgeneregulationforthymicnegativeselection AT stephanieehumbletbaron modelsofairedependentgeneregulationforthymicnegativeselection AT stephanieehumbletbaron modelsofairedependentgeneregulationforthymicnegativeselection AT jamesedooley modelsofairedependentgeneregulationforthymicnegativeselection AT jamesedooley modelsofairedependentgeneregulationforthymicnegativeselection AT adrianeliston modelsofairedependentgeneregulationforthymicnegativeselection AT adrianeliston modelsofairedependentgeneregulationforthymicnegativeselection |