CCL22-producing CD8α- myeloid dendritic cells mediate regulatory T cell recruitment in response to G-CSF treatment.
J Immunol
; 191(5): 2266-72, 2013 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-23878314
ABSTRACT
G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local recruitment of T regulatory cells (Tregs). This is an indirect effect because adoptive transfer of G-CSF-induced tolerogenic dendritic cells (DCs) promotes Treg accumulation. However, the identity of the particular DC subset and the molecule(s) mediating this effect remain unknown. We demonstrate in this study that the adoptive transfer of CD11c(high)CD8α(-) DCs isolated from pegylated G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the pancreatic recruitment of CD4(+)CD25(+)Foxp3(+) Tregs, which generated increased amounts of TGF-ß. Likewise, only CD11c(high)CD8α(-) DCs from pegG-CSF recipients secreted the chemokine CCL22 at levels that effectively attracted Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes compared with those from the spleen. Accordingly, CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes of pegG-CSF recipients were more efficient than their splenic counterparts in the recruitment of Tregs upon adoptive transfer. Predictably, CD11c(high)CD8α(-) DCs failed to recruit these Tregs both in vivo and in vitro following intracellular neutralization of CCL22. These data assign a key role to CD8α(-) DCs and CCL22 in Treg recruitment in the protection of NOD mice against type 1 diabetes following the treatment with G-CSF.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Fator Estimulador de Colônias de Granulócitos
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Linfócitos T Reguladores
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Quimiocina CCL2
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Diabetes Mellitus Tipo 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article