PI3-Kinase-γ Has a Distinct and Essential Role in Lung-Specific Dendritic Cell Development.
Fiche publication
Date publication
octobre 2015
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SCHNEIDER Christophe
Tous les auteurs :
Nobs SP, Schneider C, Dietrich MG, Brocker T, Rolink A, Hirsch E, Kopf M
Lien Pubmed
Résumé
Development of dendritic cells (DCs) commences in the bone marrow, from where pre-DCs migrate to peripheral organs to differentiate into mature DCs in situ. However, the factors that regulate organ-specific differentiation to give rise to tissue-specific DC subsets remain unclear. Here we show that the Ras-PI3Kγ-Akt-mTOR signaling axis acted downstream of FLT3L signaling and was required for development of lung CD103(+) DCs and, to a smaller extent, for lung CD11b(+) DCs, but not related DC populations in other non-lymphoid organs. Furthermore, we show that in lymphoid organs such as the spleen, DCs depended on a similar signaling network to respond to FLT3 ligand with overlapping and partially redundant roles for kinases PI3Kγ and PI3Kδ. Thus we identified PI3Kγ as an essential organ-specific regulator of lung DC development and discovered a signaling network regulating tissue-specific DC development mediated by FLT3.
Mots clés
FLT3, PI3Kγ, lung dendritic cells, tissue specificity
Référence
Immunity. 2015 Oct 20;43(4):674-89