Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling.
Immunity
; 33(4): 597-606, 2010 Oct 29.
Article
em En
| MEDLINE
| ID: mdl-20933441
ABSTRACT
Dendritic cells (DCs) comprise distinct functional subsets including CD8â» 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Transdução de Sinais
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Proteínas Serina-Treonina Quinases
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article