Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse.
Fiche publication
Date publication
novembre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GASMAN Stéphane
Tous les auteurs :
Pulecio J, Petrovic J, Prete F, Chiaruttini G, Lennon-Dumenil AM, Desdouets C, Gasman S, Burrone OR, Benvenuti F
Lien Pubmed
Résumé
The immune synapse (IS) forms as dendritic cells (DCs) and T cells interact in lymph nodes during initiation of adaptive immunity. Factors that contribute to the formation and maintenance of IS stability and function have been mostly studied in T cells, whereas little is known about events occurring during synapse formation in DCs. Here, we show that DCs activated by Toll-like receptor (TLR) agonists reorient the microtubule-organizing center (MTOC) toward the interacting T cell during antigen-specific synapse formation through a mechanism that depends on the Rho GTPase Cdc42. IL-12, a pivotal cytokine produced by DCs, is found enriched around the MTOC at early time points after TLR ligation and is dragged to the DC-T cell interface in antigen-specific synapses. Synaptic delivery of IL-12 induces activation of pSTAT4 and IFN-gamma neosynthesis in CD8(+) naive T cells engaged in antigen-specific conjugates and promotes the survival of antigen-primed T cells. We propose that DC polarization increases the local concentration of proinflammatory mediators at the IS and that this represents a new mechanism by which T cell priming is controlled.
Référence
J Exp Med. 2010 Nov 22;207(12):2719-32