Compromised central tolerance of ICA69 induces multiple organ autoimmunity.
J Autoimmun
; 53: 10-25, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25088457
ABSTRACT
For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known ß-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NOD mice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, but also in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression the heterozygous ICA69(del/wt) line and the thymic medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central negative selection of ICA69-reactive T-cells was observed in both lines. Aire-ΔICA69 mice spontaneously developed coincident autoimmune responses to the pancreas, the salivary glands, the thyroid, and the stomach. Our findings establish a direct link between compromised thymic ICA69 expression and autoimmunity against multiple ICA69-expressing organs, and identify a potential novel mechanism for the development of multi-organ autoimmune diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Doenças Autoimunes
/
Tolerância Imunológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Autoimmun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos