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Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE)
- Source :
- Journal of Autoimmunity. 86:75-92
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire.
- Subjects :
- 0301 basic medicine
Immunology
Autoimmunity
Mice, Transgenic
Thymus Gland
Biology
medicine.disease_cause
Polymyositis
Autoantigens
03 medical and health sciences
Mice
Antigen
Mice, Inbred NOD
AIRE
medicine
Immune Tolerance
Immunology and Allergy
Animals
Humans
NOD mice
Muscles
Peripheral tolerance
medicine.disease
Autoimmune regulator
Disease Models, Animal
030104 developmental biology
Diabetes Mellitus, Type 1
Organ Specificity
Autoimmune diabetes
Medullary thymic epithelial cell (mTEC)
Muscle
Central tolerance
Tolerance
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Journal of Autoimmunity
- Accession number :
- edsair.doi.dedup.....760738819875955251fb044a80cf7411