title: LAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling.
abstract: 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.
authors.affiliation: Biocenter, Division of Cell Biology, Innsbruck Medical University, Innrain 80-82, Innsbruck A6020, Austria.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Scheffler
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck A6020, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Sparber
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck A6020, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Tripp
authors.affiliation: Biocenter, Division of Cell Biology, Innsbruck Medical University, Innrain 80-82, Innsbruck A6020, Austria.
authors.forename: Caroline
authors.initials: C
authors.lastname: Herrmann
authors.affiliation: Austrian Drug Screening Institute (ADSI), Innsbruck A6020, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Humenberger
authors.affiliation: Biocenter, Division of Cell Biology, Innsbruck Medical University, Innrain 80-82, Innsbruck A6020, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Blitz
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck A6020, Austria.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Romani
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck A6020, Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.affiliation: 1] Biocenter, Division of Cell Biology, Innsbruck Medical University, Innrain 80-82, Innsbruck A6020, Austria [2] Austrian Drug Screening Institute (ADSI), Innsbruck A6020, Austria.
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Huber
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology*; D011992:Endosomes / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005838:Genotype; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: C426009:LAMTOR2 protein, mouse; D011506:Proteins; C546843:mTOR protein, mouse; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases