6533b82efe1ef96bd129429a

RESEARCH PRODUCT

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity.

Di Caro VPhillips BEngman CHarnaha JTrucco MGiannoukakis N.Antonella D'anneo

subject

Phosphatidylinositol-3-kinaseSignaling.TLROligonucleotidesImmunoregulationDendritic cells

description

Modulating PI3K at different stages of dendritic cells (DC) generation could be a novel means to balance the generation of immunosuppressive versus immunostimulatory DC. We show that PI3K inhibition during mouse DC generation in vitro results in cells that are potently immunosuppressive and characteristic of CD8alpha- CD11c+ CD11b+ DC. These DC exhibited low surface class I and class II MHC, CD40, and CD86 and did not produce TNF-alpha. In allogeneic MLR, these DC were suppressive. Although in these mixed cultures, there was no increase in the frequency of CD4+ CD25+ Foxp3+ cells, the Foxp3 content on a per cell basis was significantly increased. Sustained TLR9 signaling in the presence of PI3K inhibition during DC generation overrode the cells' suppressive phenotype.

10.1007/s12026-011-8206-1.http://hdl.handle.net/10447/73232