| First Author | Sathaliyawala T | Year | 2010 |
| Journal | Immunity | Volume | 33 |
| Issue | 4 | Pages | 597-606 |
| PubMed ID | 20933441 | Mgi Jnum | J:165522 |
| Mgi Id | MGI:4837598 | Doi | 10.1016/j.immuni.2010.09.012 |
| Citation | Sathaliyawala T, et al. (2010) Mammalian target of rapamycin controls dendritic cell development downstream of flt3 ligand signaling. Immunity 33(4):597-606 |
| abstractText | 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. |
