LAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature communications 2014-10, Vol.5 (1), p.5138, Article 5138
Hauptverfasser: Scheffler, Julia M., Sparber, Florian, Tripp, Christoph H., Herrmann, Caroline, Humenberger, Alexandra, Blitz, Johanna, Romani, Nikolaus, Stoitzner, Patrizia, Huber, Lukas A.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. LAMTOR2 is involved in mTOR and ERK signalling and plays a role in immunity, but its function in dendritic cells (DCs) is not clear. Here the authors show that deletion of LAMTOR2 in DCs results in increased mTOR signalling, accumulation of Flt3 on the cell surface and excessive DC proliferation in ageing mice.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms6138