Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).
J Autoimmun
; 86: 75-92, 2018 01.
Article
en En
| MEDLINE
| ID: mdl-28931462
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Timo
/
Factores de Transcripción
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Polimiositis
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Diabetes Mellitus Tipo 1
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Músculos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón