The Notch ligand Jagged-1 is able to induce maturation of monocyte-derived human dendritic cells.
Notch receptors play a key role in several cellular processes including differentiation, proliferation, and apoptosis. This study investigated whether the activation of Notch signaling would affect the maturation of dendritic cells (DCs). Direct stimulation of Notch signaling in DCs with a peptide ligand induced DC maturation, similar to LPS: DCs up-regulated maturation markers, produced IL-12, lost endocytosis capacity, and became able to activate allogeneic T cells. Furthermore, coculture of DCs with cells expressing Notch ligand Jagged-1 induced up-regulation of maturation markers, IL-12 production, T cell proliferative responses, and IFN-gamma production. Our data suggest that activation of Notch by Jagged-1 plays an important role in maturation of human DCs. Additionally, they reveal a novel role for Notch signaling in cell maturation events distal to the cell fate decision fork. These data may have important medical implications, since they provide new reagents to induce DC activity, which may be beneficial as adjuvants in situations where an immune response needs to be elicited, such as tumor immunotherapy.
Weijzen
Sanne
S
Cancer Immunology and Skin Cancer Programs, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA.
Velders
Markwin P
MP
Elmishad
Amira G
AG
Bacon
Patricia E
PE
Panella
Jeffrey R
JR
Nickoloff
Brian J
BJ
Miele
Lucio
L
Kast
W Martin
WM
D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D015603:Keratinocytes / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors; D014162:Transfection
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors