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Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse

2010; Rockefeller University Press; Volume: 207; Issue: 12 Linguagem: Inglês

10.1084/jem.20100007

1540-9538

Julián Pulecio, Jelena Petrovic, Francesca Prete, Giulia Chiaruttini, Ana-María Lennon-Duménil, Chantal Desdouets, Stéphane Gasman, Óscar R. Burrone, Federica Benvenuti,

Neuroinflammation and Neurodegeneration Mechanisms

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-γ 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.