Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity.
Nat Genet
; 39(3): 329-37, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17277778
ABSTRACT
Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4(+) CD25(+) regulatory T cells, which are critical for maintaining immune homeostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
/
Interleucina-2
/
Linfócitos T Reguladores
/
Diabetes Mellitus Tipo 1
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Canadá