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Publication : The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells.

First Author  Chiaruttini G Year  2016
Journal  Cell Rep Volume  14
Issue  11 Pages  2624-36
PubMed ID  26972013 Mgi Jnum  J:234824
Mgi Id  MGI:5790919 Doi  10.1016/j.celrep.2016.02.055
Citation  Chiaruttini G, et al. (2016) The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells. Cell Rep 14(11):2624-36
abstractText  Interleukin-12 (IL-12), produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs) from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells.
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