Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that iC3b is deposited at the dermal-epidermal junction of the skin following ultraviolet (UV) exposure and that it plays a role in UV-induced immunosuppression and antigenic tolerance. In vitro, iC3b differentially regulates monocyte production of interleukin-10 (IL-10) and IL-12. Additionally, iC3b arrests monocytic cell differentiation into CD1c-expressing dendritic cell (DC) precursors. The present study addresses mitogen-activated protein kinase (MAPK) signalling following the cross-linking of CR3 by its ligand iC3b with regard to monocyte differentiation and cytokine regulation. Sheep erythrocytes were coated with IgM alone (EA) or iC3b (EAiC3b) to allow for CR3 cross-linking onto monocytes. EAiC3b increased the phosphorylation (p) of extracellular signal-regulated kinase (ERK) MAPK in fresh human monocyte, particularly in monocyte-derived DC (MDDC) that were differentiated by means of GM-CSF (1000 U/ml) and IL-4 (200 U/ml) for 2 days before iC3b exposure for an additional 24 h (P=0.034, n=3). CD1a expression, induced by GM-CSF and IL-4, was inhibited by iC3b (EAiC3b vs. EA, P=0.012, n=4). Conversely, the inhibition of ERK by the specific inhibitor (PD98059), but not the p-38 inhibitor SB203580, restored CD1a expression (P=0.011, n=4) in iC3b-stimulated MDDC. Concordantly, the inhibition of ERK during iC3b exposure fully reversed the inhibition of IL-12p70 induction in MDDC by 95% (P<0.01, n=4) and decreased IL-10 production. Taken together, our data demonstrate that iC3b interferes with MDDC differentiation and IL-12 and IL-10 production is mediated via an ERK MAPK-dependent mechanism. Thus, ERK MAPK inhibition may represent a therapeutic strategy for preventing monocytic precursor diversion away from DC differentiation when monocytes enter injured tissues in which iC3b is generated, such as UV-exposed skin.
 ...
PMID:Inhibition of monocyte-derived dendritic cell differentiation and interleukin-12 production by complement iC3b via a mitogen-activated protein kinase signalling pathway. 1581 Aug 89

Integration of innate and adaptive arms of the immune response at a cellular and molecular level appears to be fundamental to the development of powerful effector functions in host defence and aberrant immune responses. Here we provide evidence that the functions of human complement activation and antigen presentation converge on dendritic cells (DCs). We show that several subsets of human DCs [i.e., monocyte derived (CD1a(+)CD14(-)), dermal (CD1a(+)DC-SIGN(+)), Langerhans (CD1a(+)Langerin(+)), myeloid (CD1c(+)CD19(-)), plamacytoid (CD45RA(+)CD123(+))] express many of the components of the classical and alternative and terminal pathways of complement. Moreover human DCs have receptors known to detect the biologically active peptides C3a and C5a (C3aR, C5aR) and the covalently bound fragments C3b and metabolites iC3b and C3d which serve in immune adhesion (i.e., CR3, CR4, CRIg). We also show that the human DC surface is characterised by membrane bound regulators of complement activation, which are also known to participate in intracellular signalling (i.e., CD46, CD55, CD59). This work provides an extensive description of complement components relevant to the integrated actions of complement and DC, illuminated by animal studies. It acts as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases.
 ...
PMID:Expression of complement components, receptors and regulators by human dendritic cells. 2139 47