Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction.
J Allergy Clin Immunol
; 121(4): 1000-5.e8, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18313135
ABSTRACT
BACKGROUND:
The mechanisms by which human dendritic cells (DCs) activate a TH1-polarizing or TH2-polarizing program are still partially unclear.OBJECTIVE:
Study of the mechanisms responsible for the TH1/TH2-polarizing activity of human circulating myeloid DCs before and after ligation of their Toll-like receptors (TLRs).METHODS:
IL-4 and IFN-gamma production by CD4+ T cells was assessed in cocultures with myeloid DCs before or after TLR triggering. Expression of Jagged-1 and Delta-4 Notch ligands and of GATA-3 and T-box expressed in T cells transcription factors was evaluated by real-time quantitative PCR. Signal transducer and activator of transcription 4 and 6 phosphorylation was assessed by flow cytometry. Knockdown of Jagged-1 or Delta-4 was performed by transfection of DCs with appropriate silencing mRNAs.RESULTS:
Myeloid immature DCs constitutively expressed Jagged-1, which induces in CD4+ T cells a TH2 polarization, as shown by Jagged-1 gene silencing. The TH2 polarization associated with high GATA-3/T-box expressed in T cells ratio and was at least partially dependent on the early induction of IL-4. Maturation of DCs by TLR ligation resulted in the reduction of Jagged-1 and upregulation of Delta-4, which was at least in part responsible for the polarization of CD4+ T cells to the TH1 phenotype.CONCLUSION:
CD4+ T-cell responses are usually characterized by a prevalent TH2 phenotype unless TLRs are triggered on DCs by microbial components.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Proteínas de Ligação ao Cálcio
/
Comunicação Celular
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Diferenciação Celular
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Células Th2
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Células Progenitoras Mieloides
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Peptídeos e Proteínas de Sinalização Intercelular
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Receptores Notch
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article