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

Abstract:

: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.

journal_name

Immunol Res

journal_title

Immunologic research

authors

Di Caro V,D'Anneo A,Phillips B,Engman C,Harnaha J,Trucco M,Giannoukakis N

doi

10.1007/s12026-011-8206-1

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

130-52

issue

2-3

eissn

0257-277X

issn

1559-0755

journal_volume

50

pub_type

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