p27(Kip1) inhibits systemic autoimmunity through the control of Treg cell activity and differentiation.
Arthritis Rheum
; 65(2): 343-54, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23124840
ABSTRACT
OBJECTIVE:
Despite the importance of Treg cells in the maintenance of immunologic tolerance, the mechanisms that control their generation and activity are unknown. Since the cell cycle inhibitor p27(Kip1) (p27) was involved in T cell anergy, we undertook this study to explore its role in both Treg cell processes.METHODS:
The development of type II collagen-induced arthritis (CIA) and lupus-like abnormalities was compared between transgenic mice overexpressing human Bcl-2 in T cells (BCL2-TgT mice) and nontransgenic mice that were deficient or not deficient in p27. The contribution of Treg cells to disease evolution was also explored. Finally, the in vitro activity of Treg cells and their differentiation from naive CD4+ cells was compared between these strains of mice.RESULTS:
BCL2-TgT mice were protected against CIA by a Treg cell-dependent mechanism. In association with this protection, the overexpression of Bcl-2 in T cells enhanced the differentiation and activity of Treg cells. Both Bcl-2 effects were independent of its antiapoptotic activity but dependent on its capacity to induce the expression of p27 that augmented the strength of transforming growth factor ß (TGFß) signaling in T cells. Accordingly, down-modulation of p27 expression in BCL2-TgT mice promoted CIA. In addition, p27 deficiency in aged C57BL/6 mice reduced the number and activity of Treg cells and induced the development of mild lupus-like abnormalities.CONCLUSION:
Our results point to p27 as a critical regulator of Treg cell differentiation and function through the positive modulation of TGFß signaling strength in T cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Autoinmunidad
/
Diferenciación Celular
/
Linfocitos T Reguladores
/
Inhibidor p27 de las Quinasas Dependientes de la Ciclina
Límite:
Animals
Idioma:
En
Revista:
Arthritis Rheum
Año:
2013
Tipo del documento:
Article
País de afiliación:
España