Snx17 is a novel regulator of antigen internalization and cross-presentation by dendritic cells

NICOLAS BLANCHARD; SOFÍA DINAMARCA; LUIS MAYORGA; CRISTINA CROCE; IGNACIO CEBRIÁN

Paraná, Entre Ríos

Congreso; SAIB - 54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2018

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Sorting nexins (SNXs) are a family of effector proteins known to regulate several features of endocytosis and membrane trafficking. They arecytoplasmic and membrane associated proteins characterized by the presence of a particular type of phox-homology (PX) domain, the SNX-PXdomain. As PX domains function mostly by binding phosphatidylinositol-3-monophosphate (PtdIns3P), SNXs are associated with PtdIns3Penrichedelements of the early endocytic network. From there, they function in diverse processes, including endocytosis, endosomal sorting,signaling and tubulation. In this study, we focus on the role of SNX17 in dendritic cells (DCs), which are the most potent antigen presenting celltype to achieve efficient cross-presentation. This immunological process is characterized by the presentation of exogenous antigens in associationwith MHC-I molecules to CD8+ T lymphocytes. Here, we identify SNX17 as a key regulator of antigen internalization and cross-presentation byDCs. By silencing the expression of SNX17 with shRNAs, we observe a significant defect in the uptake of soluble antigens (endocytosis) and 3μm latex beads (phagocytosis), as compared to control cells. Accordingly, the cross-presentation of these same antigens is hampered in SNX17knock-down DCs. Interestingly, the cell surface expression and intracellular recycling of MHC-I molecules is not affected in SNX17 deficientcells, as evaluated by flow cytometry analysis. Overall, our results provide compelling evidence that