Table.
DC Migration-Associated Molecules and Processes as Therapeutic Targets
| Target | Therapeutic Agent | Treatment | Type of DC | Species | Effect | Ref. |
|---|---|---|---|---|---|---|
| Chemokine receptors | ||||||
| CCR7 | Interferon-β | In vivo | pDC | Human | Normalized upregulation upon TLR9 stimulation | (98) |
| In vitro | BMDC | Mouse | Reduced upregulation upon maturation with pro-inflammatory cytokines, mediated through STAT-1 | (156) | ||
| In vivo | cDC, pDC | Human | No effect | (99) | ||
| CCR5 | In vivo | cDC, pDC | Human | No effect | (99) | |
| CCR7 | Natalizumab | In vivo | pDC | Human | Increased proportion of positive cells in treated vs untreated MS patients | (160) |
| CCR7 | Fingolimod | In vivo | CD11c+ DC | Mouse | Reduced expression as compared to DC of nontreated mice | (166) |
| In vitro | BMDC | Mouse | Reduced expression as compared to untreated BMDC | (166) | ||
| In vitro | moDC | Human | No effect | (163, 165) | ||
| CCR1, CCR3, CCR5, CXCR4 | In vitro | moDC | Human | No effect | (163, 165) | |
| CCR6 | Glatiramer acetate | In vivo | moDC | Human | Increased expression as compared to pretreatment levels | (157) |
| Matrix metalloproteinases | ||||||
| MMP-9 | Interferon-β | In vitro | moDC | Human | Decreased production and activity | (153) |
| In vitro | BMDC | Mouse | Abolished induction upon PGE2 stimulation, mediated through STAT-1 | (156) | ||
| Adhesion molecules | ||||||
| DC-SIGN | Interferon-β | In vitro | moDC | Human | Abolished induction during DC differentiation in vitro | (154) |
| CD62L | In vivo | cDC, pDC | Human | Reduced proportion of positive cells in treated vs nontreated MS patients | (99) | |
| VLA-4 | Natalizumab | In vivo | cDC, pDC | Human | Reduced proportion of positive cells as compared to pretreatment levels | (159) |
| In vivo | pDC | Human | Increased proportion but reduced staining intensity of positive cells in treated vs untreated MS patients | (160) | ||
| LFA-1 | In vivo | cDC | Human | Increased proportion of positive cells as compared to pretreatment levels | (159) | |
| β2-Integrin | Fingolimod | In vitro | moDC | Human | Reduced expression as compared to untreated moDC | (163) |
| αM-Integrin, PECAM-1, ICAM-1 | In vivo | CD11c+ DC | Mouse | Reduced expression as compared to untreated mice | (166) | |
| Actin polymerization | ||||||
| Actin | Fingolimod | In vitro | moDC | Human | Reduced actin polymerization | (163) |
| Signaling pathways | ||||||
| ERK1/2 | Dimethylfumarate | In vitro | BMDC | Mouse | Inhibited phosphorylation upon LPS stimulation | (170) |
| NF-κB | In vitro | BMDC | Mouse | Reduced p65 phosphorylation, resulting in reduced nuclear localization and transcriptional activity of p65 | (170) | |
BMDC, bone marrow-derived DC; CCR, C-C-chemokine receptor; CD62L, CD62 ligand; cDC, conventional DC; CXCR, C-X-C-chemokine receptor; DC-SIGN, dendritic cell-specific ICAM-grabbing nonintegrin; ERK1/2, extracellular signal-regulated kinases 1 and 2; ICAM-1, intercellular adhesion molecule-1; LFA-1, lymphocyte function-associated antigen-1; MMP-9, matrix metalloproteinase 9; moDC, monocyte-derived DC; NF-κB, nuclear factor kappa-B; pDC, plasmacytoid DC; PECAM-1, platelet and endothelial cell adhesion molecule-1; PGE2, prostaglandin E2; STAT-1, signal transducer and activator of transcription 1; TLR9, Toll-like receptor-9; VLA-4, very late antigen-4.