1. The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells
- Author
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Federica Benvenuti, Sabina Müller, Giulia Maria Piperno, Mabel Jouve, Gabriele Baj, Salvatore Valitutti, Paola Larghi, Francesca De Nardi, Thierry Galli, Andrew A. Peden, Giulia Chiaruttini, Chiaruttini, Giulia, Piperno, GIULIA MARIA, Jouve, Mabel, De Nardi, Francesca, Larghi, Paola, Peden, Andrew A., Baj, Gabriele, Müller, Sabina, Valitutti, Salvatore, Galli, Thierry, Benvenuti, Federica, International Centre for Genetic Engineering and Biotechnology (ICGEB) (Trieste), Génétique et Biologie du Développement, Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Pathophysiology and Transplantation, University of Milan, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi,', Department of Biomedical Science, University of Sheffield [Sheffield]--Centre for Membrane Interactions and Dynamics, Department of Life Sciences, University of Trieste, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), INSERM ERL U950, Membrane Traffic in Neuronal and Epithelial Morphogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Associazione Italiana Ricerca Cancro IG9076, IG2013 14414, Worldwide Cancer Research 14-0320, AIRC, ICGEB, Telethon grant GGP14281, Agence Nationale de la Recherche (ANR-13-BSV2-0018-02), Fondation ARC, ANR-10-INBS-04-01/10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre for Membrane Interactions and Dynamics -University of Sheffield [Sheffield], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Trieste = University of Trieste, and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Genetics and Molecular Biology (all) ,0301 basic medicine ,Male ,Cellular differentiation ,T-Lymphocytes ,Cell ,Bone Marrow Cells ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Biochemistry ,Time-Lapse Imaging ,General Biochemistry, Genetics and Molecular Biology ,Exocytosis ,Article ,Immunological synapse ,R-SNARE Proteins ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,RNA, Small Interfering ,lcsh:QH301-705.5 ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,Mice, Knockout ,Microscopy, Confocal ,Microscopy, Video ,Biochemistry, Genetics and Molecular Biology (all) ,Vesicle ,Phosphotransferases ,rab7 GTP-Binding Proteins ,Cell Differentiation ,Dendritic Cells ,16. Peace & justice ,Interleukin-12 ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocytic vesicle ,lcsh:Biology (General) ,rab GTP-Binding Proteins ,Synapses ,Interleukin 12 ,RNA Interference ,Intracellular ,030215 immunology - Abstract
Summary 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., Graphical Abstract, Highlights • Intracellular trafficking of IL-12 in dendritic cells is mediated by the SNARE VAMP7 • VAMP7 is required for optimal secretion of IL-12 in the extracellular space • IL-12/VAMP7+ vesicles gather at the immune synapse • VAMP7 controls synaptic release of IL-12 and IFN-γ production in T cells, Efficient priming of T cells requires antigenic and soluble cytokine signals. Chiaruttini et al. analyze the intracellular trafficking pathway of IL-12 in dendritic cells and identify the SNARE VAMP7 as a key regulator of cytokine release and T cell activation.
- Published
- 2016
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