| First Author | Scheffler JM | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5138 | PubMed ID | 25336251 |
| Mgi Jnum | J:225705 | Mgi Id | MGI:5694043 |
| Doi | 10.1038/ncomms6138 | Citation | Scheffler JM, et al. (2014) LAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling. Nat Commun 5:5138 |
| abstractText | The receptor tyrosine kinase Flt3 and its ligand are crucial for dendritic cell (DC) homeostasis by activating downstream effectors including mammalian target of Rapamycin (mTOR) signalling. LAMTOR2 is a member of the Ragulator/LAMTOR complex known to regulate mTOR and extracellular signal-regulated kinase activation on the late endosome as well as endosomal biogenesis. Here we show in mice that conditional ablation of LAMTOR2 in DCs results in a severe disturbance of the DC compartment caused by accumulation of Flt3 on the cell surface. This results in an increased downstream activation of the AKT/mTOR signalling pathway and subsequently to a massive expansion of conventional DCs and plasmacytoid DCs in ageing mice. Finally, we can revert the symptoms in vivo by inhibiting the activation of Flt3 and its downstream target mTOR. |
