Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model.
Am J Pathol
; 185(11): 2886-97, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26343329
ABSTRACT
Neonatal thymectomy in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3(+) regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal thymectomy remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjögren syndrome model of NFS/sld mice that underwent neonatal thymectomy. The ratio of Treg cells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-ß (TGF-ß) using naive T cells from Sjögren syndrome model mice was severely impaired. The mRNA expression of TGF-ß receptor I and II and Smad3 and -4 in the TGF-ß-induced signal transduction pathway of Treg cells in this Sjögren syndrome model were lower than those of control mice. In addition, Treg cells in this Sjögren syndrome model exhibited an interferon-γ-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Factor de Crecimiento Transformador beta
/
Interferón gamma
/
Proteínas Serina-Treonina Quinasas
/
Linfocitos T Reguladores
/
Receptores de Factores de Crecimiento Transformadores beta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article