PMID- 19171874
OWN - NLM
STAT- MEDLINE
DCOM- 20090507
LR  - 20211028
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 15
DP  - 2009 Apr 9
TI  - C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 
      costimulatory pathway on dendritic cells.
PG  - 3485-93
LID - 10.1182/blood-2008-06-164392 [doi]
AB  - 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.
FAU - Baruah, Paramita
AU  - Baruah P
AD  - Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial 
      College London, London, United Kingdom.
FAU - Dumitriu, Ingrid E
AU  - Dumitriu IE
FAU - Malik, Talat H
AU  - Malik TH
FAU - Cook, H Terence
AU  - Cook HT
FAU - Dyson, Julian
AU  - Dyson J
FAU - Scott, Diane
AU  - Scott D
FAU - Simpson, Elizabeth
AU  - Simpson E
FAU - Botto, Marina
AU  - Botto M
LA  - eng
GR  - BB/F020732/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - 071467/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090126
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CD40 Antigens)
RN  - 0 (Calreticulin)
RN  - 0 (Toll-Like Receptors)
RN  - 187348-17-0 (Interleukin-12)
RN  - 80295-33-6 (Complement C1q)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Apoptosis/immunology
MH  - CD40 Antigens/*metabolism
MH  - Calreticulin/metabolism
MH  - Cell Communication/immunology
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Complement C1q/genetics/*metabolism/pharmacology
MH  - Dendritic Cells/cytology/drug effects/*metabolism
MH  - Female
MH  - Humans
MH  - Interferon-gamma/*metabolism
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Transfusion
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phagocytosis/immunology
MH  - Spleen/cytology
MH  - Th1 Cells/*cytology/metabolism
MH  - Toll-Like Receptors/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2009/01/28 09:00
MHDA- 2009/05/08 09:00
CRDT- 2009/01/28 09:00
PHST- 2009/01/28 09:00 [entrez]
PHST- 2009/01/28 09:00 [pubmed]
PHST- 2009/05/08 09:00 [medline]
AID - S0006-4971(20)39346-0 [pii]
AID - 10.1182/blood-2008-06-164392 [doi]
PST - ppublish
SO  - Blood. 2009 Apr 9;113(15):3485-93. doi: 10.1182/blood-2008-06-164392. Epub 2009 
      Jan 26.