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AIRE deficiency, from preclinical models to human APECED disease
- Source :
- Disease Models & Mechanisms, article-version (VoR) Version of Record, Disease Models & Mechanisms, Cambridge Company of Biologists, 2021, 14 (2), ⟨10.1242/dmm.046359⟩, Disease Models & Mechanisms, Vol 14, Iss 2 (2021), Disease Models & Mechanisms, 2021, 14 (2), ⟨10.1242/dmm.046359⟩
- Publication Year :
- 2021
- Publisher :
- The Company of Biologists Ltd, 2021.
-
Abstract
- 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.<br />Summary: In this Review, we discuss the in vivo and in vitro models available to study AIRE deficiency, and how they may contribute to restoring immunological tolerance in APECED patients.
- Subjects :
- 0301 basic medicine
Keratinocytes
Organoid
[SDV]Life Sciences [q-bio]
Medicine (miscellaneous)
lcsh:Medicine
Disease
Review
Autoantigens
Mice
0302 clinical medicine
Immunology and Microbiology (miscellaneous)
Polyendocrinopathies, Autoimmune
Thymocytes
Autoimmune polyendocrinopathy
Autoimmune regulator
Phenotype
3. Good health
Organoids
[SDV] Life Sciences [q-bio]
[SDV.IMM]Life Sciences [q-bio]/Immunology
Immunotherapy
lcsh:RB1-214
[SDV.IMM] Life Sciences [q-bio]/Immunology
Neuroscience (miscellaneous)
Thymus Gland
Biology
General Biochemistry, Genetics and Molecular Biology
Autoimmune Diseases
03 medical and health sciences
AIRE
Knockout model
medicine
Immune Tolerance
lcsh:Pathology
Animals
Humans
Point Mutation
APS-1
Gene
Autoantibodies
Autoimmune disease
lcsh:R
Autoantibody
Epithelial Cells
mTEC
medicine.disease
Coculture Techniques
Rats
Disease Models, Animal
030104 developmental biology
Immunology
Mutation
Ex vivo
030215 immunology
Transcription Factors
APECED
Subjects
Details
- Language :
- English
- ISSN :
- 17548411 and 17548403
- Volume :
- 14
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Disease Models & Mechanisms
- Accession number :
- edsair.doi.dedup.....7941f2269e715da4dc0e370581002810