Cutting edge: Plasmacytoid dendritic cells induce IL-10 production in T cells via the Delta-like-4/Notch axis.
Proinflammatory Th1 cells can produce large amounts of the immunosuppressive cytokine IL-10, thereby facilitating the self-limitation of inflammatory responses. Recently, we identified the Notch pathway as a main regulator of IL-10 production by Th1 cells. In this study, we show that plasmacytoid dendritic cells (pDCs), by means of their unique high-level expression of the Notch ligand Delta-like (Dll)-4, activate the Notch receptor on T cells to induce robust IL-10 production in vitro and in vivo. pDCs display a distinct pattern of Notch ligands compared with conventional dendritic cells, marked by the constitutive expression of Dll-4, the only Notch ligand to induce IL-10 expression in vivo, and Dll-1, while at the same time lacking the expression of Jagged. We provide a new mechanism for IL-10 induction by pDCs underlining the importance of the Dll-4/Notch axis in the regulation of inflammatory T cell responses.
Kassner
Nadine
N
Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
Krueger
Manuela
M
Yagita
Hideo
H
Dzionek
Andrzej
A
Hutloff
Andreas
A
Kroczek
Richard
R
Scheffold
Alexander
A
Rutz
Sascha
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051880:Receptors, Notch / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; D016753:Interleukin-10