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Datasets  >  signalling dataset  >  Activation of mouse DC: ind...

Activation of mouse DC: induction of endogenous IL-10 production by DC subsets accounts for their low levels of IL-12p70 production

signalling dataset

Our lab has data available on the effect of endogenous IL-10 production by DC subsets resulting in low levels of IL-12p70 production in mice.

We have shown that plasmacytoid pDC respond to both CpG and the TLR-7 ligand R848 to produce very high levels of IL-12p70 (in the ng/ml range per 5 x 105 cells/ml) and IFN-gamma. However, BM-myeloid and splenic CD8alpha+ DC produced at least fivefold less IL-12p70, and CD8alpha- DC produced undetectable levels of IL-12p70 upon stimulation with CpG.

We show that induction of endogenous IL-10 production by these latter DC subsets accounts for their low levels of IL-12p70 production, and since the plasmacytoid pDC do not produce IL-10 this explains their production of high levels of IL-12p70. Neither endogenous IL-10 production nor a lack of TLR9 expression can however explain the lack of IFN-alpha production by the myeloid and splenic CD8alpha+ and CD8alpha- DC. These data suggest that different pathogens may trigger differential cytokine production as a result of their engagement of distinct TLRs on DC, and in addition by their differential ability to induce IL-10 or IFN-alpha in different DC. This work has now been published in the J. Immunology (Boonstra, Rajsbaum et al, 2006) and the microarray studies as discussed above are based on this study but including the plasmacytoid DC and will continue this project in collaboration with P. Ricciardi-Castagnoli, UNIMIB.







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