Cargando…
AIRE deficiency, from preclinical models to human APECED disease
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare life-threatening autoimmune disease that attacks multiple organs and has its onset in childhood. It is an inherited condition caused by a variety of mutations in the autoimmune regulator (AIRE) gene that encodes a prot...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875492/ https://www.ncbi.nlm.nih.gov/pubmed/33729987 http://dx.doi.org/10.1242/dmm.046359 |
_version_ | 1783649779788546048 |
---|---|
author | Besnard, Marine Padonou, Francine Provin, Nathan Giraud, Matthieu Guillonneau, Carole |
author_facet | Besnard, Marine Padonou, Francine Provin, Nathan Giraud, Matthieu Guillonneau, Carole |
author_sort | Besnard, Marine |
collection | PubMed |
description | Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare life-threatening autoimmune disease that attacks multiple organs and has its onset in childhood. It is an inherited condition caused by a variety of mutations in the autoimmune regulator (AIRE) gene that encodes a protein whose function has been uncovered by the generation and study of Aire-KO mice. These provided invaluable insights into the link between AIRE expression in medullary thymic epithelial cells (mTECs), and the broad spectrum of self-antigens that these cells express and present to the developing thymocytes. However, these murine models poorly recapitulate all phenotypic aspects of human APECED. Unlike Aire-KO mice, the recently generated Aire-KO rat model presents visual features, organ lymphocytic infiltrations and production of autoantibodies that resemble those observed in APECED patients, making the rat model a main research asset. In addition, ex vivo models of AIRE-dependent self-antigen expression in primary mTECs have been successfully set up. Thymus organoids based on pluripotent stem cell-derived TECs from APECED patients are also emerging, and constitute a promising tool to engineer AIRE-corrected mTECs and restore the generation of regulatory T cells. Eventually, these new models will undoubtedly lead to main advances in the identification and assessment of specific and efficient new therapeutic strategies aiming to restore immunological tolerance in APECED patients. |
format | Online Article Text |
id | pubmed-7875492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-78754922021-02-11 AIRE deficiency, from preclinical models to human APECED disease Besnard, Marine Padonou, Francine Provin, Nathan Giraud, Matthieu Guillonneau, Carole Dis Model Mech Review Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare life-threatening autoimmune disease that attacks multiple organs and has its onset in childhood. It is an inherited condition caused by a variety of mutations in the autoimmune regulator (AIRE) gene that encodes a protein whose function has been uncovered by the generation and study of Aire-KO mice. These provided invaluable insights into the link between AIRE expression in medullary thymic epithelial cells (mTECs), and the broad spectrum of self-antigens that these cells express and present to the developing thymocytes. However, these murine models poorly recapitulate all phenotypic aspects of human APECED. Unlike Aire-KO mice, the recently generated Aire-KO rat model presents visual features, organ lymphocytic infiltrations and production of autoantibodies that resemble those observed in APECED patients, making the rat model a main research asset. In addition, ex vivo models of AIRE-dependent self-antigen expression in primary mTECs have been successfully set up. Thymus organoids based on pluripotent stem cell-derived TECs from APECED patients are also emerging, and constitute a promising tool to engineer AIRE-corrected mTECs and restore the generation of regulatory T cells. Eventually, these new models will undoubtedly lead to main advances in the identification and assessment of specific and efficient new therapeutic strategies aiming to restore immunological tolerance in APECED patients. The Company of Biologists Ltd 2021-02-05 /pmc/articles/PMC7875492/ /pubmed/33729987 http://dx.doi.org/10.1242/dmm.046359 Text en © 2021. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Review Besnard, Marine Padonou, Francine Provin, Nathan Giraud, Matthieu Guillonneau, Carole AIRE deficiency, from preclinical models to human APECED disease |
title | AIRE deficiency, from preclinical models to human APECED disease |
title_full | AIRE deficiency, from preclinical models to human APECED disease |
title_fullStr | AIRE deficiency, from preclinical models to human APECED disease |
title_full_unstemmed | AIRE deficiency, from preclinical models to human APECED disease |
title_short | AIRE deficiency, from preclinical models to human APECED disease |
title_sort | aire deficiency, from preclinical models to human apeced disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875492/ https://www.ncbi.nlm.nih.gov/pubmed/33729987 http://dx.doi.org/10.1242/dmm.046359 |
work_keys_str_mv | AT besnardmarine airedeficiencyfrompreclinicalmodelstohumanapeceddisease AT padonoufrancine airedeficiencyfrompreclinicalmodelstohumanapeceddisease AT provinnathan airedeficiencyfrompreclinicalmodelstohumanapeceddisease AT giraudmatthieu airedeficiencyfrompreclinicalmodelstohumanapeceddisease AT guillonneaucarole airedeficiencyfrompreclinicalmodelstohumanapeceddisease |