PD-L1 blockade overrides Salmonella typhimurium-mediated diabetes prevention in NOD mice: no role for Tregs.
Eur J Immunol
; 41(10): 2966-76, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21792877
Increasingly, evidence suggests that there is a strong environmental component to the development of the autoimmune disease type 1 diabetes. Our previous data showed that NOD mice are protected from developing diabetes after infection with Salmonella typhimurium and there is some evidence that changes within the DC compartment play a crucial role in this protective effect. This paper further characterises this Salmonella-modulated protective phenotype. We find that, contrary to other infection-mediated models of type 1 diabetes protection, there was no expansion of Foxp3(+) Tregs. Furthermore, transcriptome analysis of DCs identified a distinct Salmonella-induced signature in which the inhibitory receptor PD-L1 was up-regulated. This was confirmed by flow cytometry. In vivo blockade of the PD1/PD-L1 interaction was found to ablate the protective function of Salmonella infection. These data provide evidence for a novel regulatory DC phenotype proficient at controlling autoreactive T cells for an extended duration in the NOD mouse model of diabetes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Salmonelose Animal
/
Salmonella typhimurium
/
Linfócitos T Reguladores
/
Diabetes Mellitus Tipo 1
/
Antígeno B7-H1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article