LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors.
Dendritic cells (DC) obtained by culturing myeloid precursors in GM-CSF undergo maturation and induce an efficient T cell response when stimulated with microbial products. DC precursors themselves also recognize microbial products, and it remains unclear how these stimulated DC precursors modulate the immune response. We show here that M-CSF-conditioned human DC precursors responded to LPS, Mycobacteria bovis, and inflammatory cytokines by a rapid and robust production of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from converting into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stimulation concomitant with DC differentiation gave rise to immature DC, which were tolerant to a secondary LPS exposure. Furthermore, the LPS-activated DC precursors reduced bystander DC maturation and anti-CD3/CD28-triggered T cell activation. These data suggest that when exposed to inflammatory or microbial signals, M-CSF-conditioned DC precursors can participate in the modulation of inflammation and immune response by rapid release of IL-10.
Kwan
Wing-Hong
WH
INSERM UMRS 872, Université Pierre et Marie Curie-Paris 6, Université René Descartes-Paris 5, Centre de Recherches Biomédicales des Cordeliers, Paris, France. wing-hong.kwan@u255.bhdc.jussieu.fr
Boix
Charlotte
C
Gougelet
Nicolas
N
Fridman
Wolf H
WH
Mueller
Chris G F
CG
D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007109:Immunity; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D022423:Myeloid Cells / Q000166:cytology
D016207:Cytokines; C508609:IL10 protein, human; D008070:Lipopolysaccharides; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor