Cutting edge: Notch signaling induces a distinct cytokine profile in dendritic cells that supports T cell-mediated regulation and IL-2-dependent IL-17 production.
Recently it has been shown that dendritic cells (DC) express both Notch and Notch ligands, allowing for the possibility that Notch signaling may influence their maturation. We show that although both Jagged (Jgd) and Delta-like (DlL) ligands were able to activate the canonical Notch pathway in mouse DC, only Jgd1 could induce the production of certain cytokines. Maturation of DC via Jgd1 resulted in an entirely different maturation program from that induced through TLR (via LPS) signaling, promoting the production of high levels of IL-2 and IL-10. DC matured by Jgd1 (Jgd1-conditioned DC) promoted the survival and proliferation of CD4(+)CD25(+) regulatory T cells that were able to suppress efficiently the proliferation of CD25(-) cells. Further, CD25(+) cells cultured with Jgd1-conditioned DC produced very high levels of IL-17 in an IL-2-dependent fashion. Our data suggest a new and important role for the Notch pathway in the regulation of the DC phenotype.
Bugeon
Laurence
L
Department of Life Sciences, Division of Cell and Molecular Biology, Centre for Integrative Systems Biology at Imperial College, Imperial College, London, United Kingdom.
Gardner
Leanne M
LM
Rose
Anna
A
Gentle
Madeleine
M
Dallman
Margaret J
MJ
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D051880:Receptors, Notch / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D002135:Calcium-Binding Proteins; D016207:Cytokines; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D007376:Interleukin-2; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins