Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction.
Eur J Immunol
; 43(1): 182-7, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23161436
ABSTRACT
Notch1 signaling is involved in regulatory T (Treg)-cell differentiation. We previously demonstrated that, when cocultured with CD3(+) cells, mesenchymal stem cells (MSCs) induced a T-cell population with a regulatory phenotype. Here, we investigated the molecular mechanism underlying MSC induction of human Treg cells. We show that the Notch1 pathway is activated in CD4(+) T cells cocultured with MSCs. Inhibition of Notch1 signaling through GSI-I or the Notch1 neutralizing antibody reduced expression of HES1 (the Notch1 downstream target) and the percentage of MSC-induced CD4(+) CD25(high) FOXP3(+) cells in vitro. Moreover, we demonstrate that FOXP3 is a downstream target of Notch signaling in human cells. No crosstalk between Notch1 and TGF-ß signaling pathways was observed in our experimental system. Together, these findings indicate that activation of the Notch1 pathway is a novel mechanism in the human Treg-cell induction mediated by MSCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
/
Linfócitos T Reguladores
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Fatores de Transcrição Forkhead
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Receptor Notch1
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Células-Tronco Mesenquimais
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article