C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells.
Blood
; 113(15): 3485-93, 2009 Apr 09.
Article
em En
| MEDLINE
| ID: mdl-19171874
ABSTRACT
Dendritic cells (DCs) are known to produce C1q, the initiator of the classical complement pathway. We demonstrate that murine DCs deficient in C1q (C1qa(-/-)) are poorer than wild-type (WT) DCs at eliciting the proliferation and Th1 differentiation of antigen-specific T cells. These defects result from decreased production of IL-12p70 by C1qa(-/-) DCs and impaired expression of costimulatory molecules CD80 and CD86 in response to CD40 ligation. The defective production of IL-12p70 and the reduced expression of CD80 and CD86 by C1qa(-/-) DCs were specifically mediated via CD40 ligation, as normal levels of IL-12p70 and CD80/86 were observed after ligation of Toll-like receptors (TLRs) on C1qa(-/-) DCs. CD40 ligation on C1qa(-/-) DCs, but not TLR ligation, results in decreased phosphorylation of p38 and ERK1/2 kinases. A strong colocalization of CD40 and C1q was observed by confocal microscopy upon CD40 ligation (but not TLR ligation) on DCs. Furthermore, human DCs from 2 C1q-deficient patients were found to have impaired IL-12p70 production in response to CD40L stimulation. Our novel data suggest that C1q augments the production of IL-12p70 by mouse and human DCs after CD40 triggering and plays important roles in sustaining the maturation of DCs and guiding the activation of T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Complemento C1q
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Interferon gama
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Células Th1
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Antígenos CD40
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido