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- W2065607560 endingPage "1682" @default.
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- W2065607560 abstract "Abstract Dendritic cell (DC) homeostasis, like all mature blood cells, is maintained via hierarchal generation from hematopoietic precursors; however, little is known about the regulatory mechanisms governing DC generation. Here, we show that prostaglandin E2 (PGE2) is required for optimal Flt3 ligand–mediated DC development and regulates expression of the Flt3 receptor on DC-committed progenitor cells. Inhibition of PGE2 biosynthesis reduces Flt3-mediated activation of STAT3 and expression of the antiapoptotic protein survivin, resulting in increased apoptosis of DC-committed progenitor cells. Reduced DC development caused by diminished PGE2 signaling is reversed by overexpression of Flt3 or survivin in DC progenitors and conversely is mimicked by STAT3 inhibition. PGE2 regulation of DC generation is specifically mediated through the EP1 and EP3 G protein PGE2 receptors. These studies define a novel DC progenitor regulatory pathway in which PGE2 signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal DC progenitor survival and DC development in vivo." @default.
- W2065607560 created "2016-06-24" @default.
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- W2065607560 date "2012-02-16" @default.
- W2065607560 modified "2023-09-29" @default.
- W2065607560 title "Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells" @default.
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- W2065607560 doi "https://doi.org/10.1182/blood-2011-03-342428" @default.
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