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J Immunol. 2010 Aug 15;185(4):2125-33. doi: 10.4049/jimmunol.0903793. Epub 2010 Jul 19.

Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways.

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The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.


IL-12 is such a pivotal cytokine that it has been called the third signal for T cell activation, TCR engagement being the first and costimulation being the second. It has been generally viewed that the resident CD8(+) dendritic cell (DC) subset is the predominant IL-12-producing cell type. In this study, we found, although this is so under steady state conditions, under inflammatory conditions monocyte-derived DC (mDC) became a major cell type producing IL-12. Depletion of either type of DC resulted in reduced production of IL-12 in vivo. For CD8(+) DC, IL-12 production could be stimulated by various pathways viz. signaling through MyD88, Trif, or nucleotide-binding oligomerization domain (Nod)-like receptors. In contrast, for mDC, IL-12 production was mainly dependent on MyD88 signaling. Thus, conventional DCs and mDCs use different pathways to regulate IL-12 production.

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