rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
15
|
pubmed:dateCreated |
2009-4-10
|
pubmed:abstractText |
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.
|
pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
1528-0020
|
pubmed:author |
|
pubmed:issnType |
Electronic
|
pubmed:day |
9
|
pubmed:volume |
113
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
3485-93
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:19171874-Animals,
pubmed-meshheading:19171874-Antigen Presentation,
pubmed-meshheading:19171874-Antigens, CD40,
pubmed-meshheading:19171874-Apoptosis,
pubmed-meshheading:19171874-Calreticulin,
pubmed-meshheading:19171874-Cell Communication,
pubmed-meshheading:19171874-Cell Differentiation,
pubmed-meshheading:19171874-Cells, Cultured,
pubmed-meshheading:19171874-Complement C1q,
pubmed-meshheading:19171874-Dendritic Cells,
pubmed-meshheading:19171874-Female,
pubmed-meshheading:19171874-Humans,
pubmed-meshheading:19171874-Interferon-gamma,
pubmed-meshheading:19171874-Interleukin-12,
pubmed-meshheading:19171874-Lymphocyte Transfusion,
pubmed-meshheading:19171874-Male,
pubmed-meshheading:19171874-Mice,
pubmed-meshheading:19171874-Mice, Mutant Strains,
pubmed-meshheading:19171874-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:19171874-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:19171874-Phagocytosis,
pubmed-meshheading:19171874-Spleen,
pubmed-meshheading:19171874-Th1 Cells,
pubmed-meshheading:19171874-Toll-Like Receptors,
pubmed-meshheading:19171874-p38 Mitogen-Activated Protein Kinases
|
pubmed:year |
2009
|
pubmed:articleTitle |
C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells.
|
pubmed:affiliation |
Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College London, London, United Kingdom.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|