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Immunity. 2010 Oct 29;33(4):597-606. doi: 10.1016/j.immuni.2010.09.012. Epub 2010 Oct 7.

Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling.

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  • 1Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

Abstract

Dendritic cells (DCs) comprise distinct functional subsets including CD8⁻ and CD8(+) classical DCs (cDCs) and interferon-secreting plasmacytoid DCs (pDCs). The cytokine Flt3 ligand (Flt3L) controls the development of DCs and is particularly important for the pDC and CD8(+) cDC and their CD103(+) tissue counterparts. We report that mammalian target of rapamycin (mTOR) inhibitor rapamycin impaired Flt3L-driven DC development in vitro, with the pDCs and CD8(+)-like cDCs most profoundly affected. Conversely, deletion of the phosphoinositide 3-kinase (PI3K)-mTOR negative regulator Pten facilitated Flt3L-driven DC development in culture. DC-specific Pten targeting in vivo caused the expansion of CD8(+) and CD103(+) cDC numbers, which was reversible by rapamycin. The increased CD8(+) cDC numbers caused by Pten deletion correlated with increased susceptibility to the intracellular pathogen Listeria. Thus, PI3K-mTOR signaling downstream of Flt3L controls DC development, and its restriction by Pten ensures optimal DC pool size and subset composition.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:
20933441
[PubMed - indexed for MEDLINE]
PMCID:
PMC2966531
Free PMC Article
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