LPS induces rapid IL-10 release by M-CSF-conditioned, tolerogenic dendritic cell precursors

Abstract: Dendritic cells (DC) obtained by cultur-ing myeloid precursors in GM-CSF undergo matu-ration 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 pre-cursors modulate the immune response. We show here that M-CSF-conditioned human DC precur-sors respond to LPS, Mycobacteria bovis, and in-flammatory cytokines by a rapid and robust pro-duction of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from convert-ing into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stim-ulation 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-con-ditioned DC precursors can participate in the mod-ulation of inflammation and immune response b