IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Critical role for sorting nexin proteins during antigen cross-presentation by dendritic cells
Autor/es:
SOFÍA DINAMARCA; NICOLAS BLANCHARD; ANNA SALVIONI; IGNACIO CEBRIÁN; CRISTINA CROCE; LUIS MAYORGA
Lugar:
San Miguel de Tucumán
Reunión:
Congreso; LXVII Reunión Científica Anual de la SAI; 2019
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Sorting nexin (SNX) proteins are involved in diverse processes of the endocytic pathway, including endocytosis, endosomal sorting, signalling and tubulation. SNXs are characterized by the presence of a particular type of phox-homology domain that operates mostly by binding phosphatidylinositol-3-monophosphate (PtdIns3P). Therefore, SNX proteins are associated with PtdIns3P-enriched elements of the early endocytic network and from there they coordinate many endosomal functions. In this study, we focus on the role of SNX17 during antigen cross-presentation, the immunological process that triggers CD8+ T responses against exogenous antigens, such as different types of pathogens and tumours. Particularly, SNX17 has been involved in the intracellular recycling of several integrins and receptors, including the transport of the TCR towards the immunological synapse in T lymphocytes. Here, we address the role of SNX17 in dendritic cells (DCs), and we identify this molecule as a key regulator of integrin recycling, actin remodelling, antigen internalization and cross-presentation. We observe that SNX17 localizes mainly in early endosomal compartments and is rapidly recruited to DC phagosomes. Our results demonstrate that the silencing of SNX17 expression in DCs severely affects the uptake of soluble and particulate antigens, delays phagosomal maturation, impairs the recycling capacity of the integrin CD11b and blocks actin remodelling. As excepted after all these functional abnormalities, the knock-down of SNX17 also hampered the antigen cross-presentation ability of DCs. Our findings provide compelling evidence that SNX17 plays a central role in endosomal recycling and antigen uptake, crucial events for an efficient cross-presentation by DCs.