title: The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells.
abstract: 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.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Chiaruttini
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Piperno
authors.affiliation: Génétique et Biologie du Développement, UMR 3215, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Mabel
authors.initials: M
authors.lastname: Jouve
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nardi
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, via F. Sforza 35, 20122 Milan, Italy; Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Larghi
authors.affiliation: Centre for Membrane Interactions and Dynamics, Department of Biomedical Science, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Peden
authors.affiliation: Life Sciences Department, University of Trieste, via Giorgieri 5, 34127 Trieste, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.affiliation: Centre de Physiopathologie Toulouse-Purpan, Toulouse, INSERM UMR 1043, Toulouse 31300, France.
authors.forename: Sabina
authors.initials: S
authors.lastname: Müller
authors.affiliation: Centre de Physiopathologie Toulouse-Purpan, Toulouse, INSERM UMR 1043, Toulouse 31300, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.affiliation: Institut Jacques Monod, UMR 7592, Centre National de la Recherche Scientifique, Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France; Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, 75013 Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Galli
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy. Electronic address: benvenuti@icgeb.org.
authors.forename: Federica
authors.initials: F
authors.lastname: Benvenuti
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005089:Exocytosis; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D010770:Phosphotransferases / Q000378:metabolism; D050683:R-SNARE Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D059008:Time-Lapse Imaging; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: C492236:Cdk5r1 protein, mouse; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; C496927:Sybl1 protein, mouse; D000090802:rab7 GTP-Binding Proteins; D018664:Interleukin-12; D010770:Phosphotransferases; D020691:rab GTP-Binding Proteins