Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-11-5
pubmed:abstractText
Regulation of T cell immunity by C5a has been suggested from recent studies. However, the underlying mechanisms, particularly the involved cells and biochemical basis, are not well defined. In this study, the direct modulation of dendritic cell (DC) activation and its function in T cell stimulation by C5a-C5aR interaction and the involved signaling pathways were investigated. We show that DCs from C5aR(-/-) mice and normal DCs treated with C5aR antagonist have less-activated phenotype characterized with increased IL-10 and decreased IL-12p70 production in response to LPS stimulation, lowered surface expression of MHC class II, B7.2, and consequently have reduced capacity to stimulate allospecific T cells. Conversely, C5a stimulation up-regulates DC activation and its function in allostimulation. Furthermore, stimulation of C5aR mediates the inhibition of cAMP production and protein kinase A activity and is involved in activation of PI3K/AKT and NF-kappaB signaling in DCs. These results demonstrate that C5a acts directly on C5aR expressed on DCs resulting in the cell activation and subsequently enhances its capacity for allospecific T cell stimulation. It also suggests that NF-kappaB signaling induced by down-regulation of cAMP/ protein kinase A pathway and up-regulation of PI3K/AKT pathway following C5a stimulation may contribute to up-regulation of DC function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6058-68
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19864610-Animals, pubmed-meshheading:19864610-CD4-Positive T-Lymphocytes, pubmed-meshheading:19864610-Complement C5a, pubmed-meshheading:19864610-Cyclic AMP, pubmed-meshheading:19864610-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:19864610-Dendritic Cells, pubmed-meshheading:19864610-Interleukin-10, pubmed-meshheading:19864610-Interleukin-12, pubmed-meshheading:19864610-Isoantigens, pubmed-meshheading:19864610-Lipopolysaccharides, pubmed-meshheading:19864610-MAP Kinase Signaling System, pubmed-meshheading:19864610-Mice, pubmed-meshheading:19864610-Mice, Inbred BALB C, pubmed-meshheading:19864610-Mice, Inbred C57BL, pubmed-meshheading:19864610-Mice, Knockout, pubmed-meshheading:19864610-NF-kappa B, pubmed-meshheading:19864610-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19864610-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19864610-Receptor, Anaphylatoxin C5a, pubmed-meshheading:19864610-Signal Transduction, pubmed-meshheading:19864610-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Dendritic cell function in allostimulation is modulated by C5aR signaling.
pubmed:affiliation
Complement Laboratory, MRC Centre for Transplantation, King's College London, School of Medicine at Guy's Hospital, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't