Targeting dendritic cells for the treatment of autoimmune disorders

tIn the last decades, it has been recognized that extracellular vesicles (EVs) are not only cell debris withno biological role, but instead they play a key role in information exchange between cells either in healthand disease conditions. EVs exhibit indeed their biological role in a pleiotropic manner. They can mod-ulate immune responses through the activation, transfer or removal of surface receptors on target cells,the removal of cytolytic components such as membrane attack complexes, and the transfer of signal-ing molecules/effectors, such as nucleic acid species, infectious particles, and oncogenes. Among thenaturally-derived nanoparticles that have been developed in the last years, stimuli responsive exosomesdrew special attention since they intrinsically possess many attributes of a desirable drug delivery system.Their small size allows them to bypass the mononuclear phagocytic system (MPS) clearance, thereby pro-longing their circulation time for passive targeting to inflammatory tissues. Moreover, they can delivertheir cargo directly into the cytosol, avoiding the lysosomal/endosomal pathway and thus, increasingthe transfection efficiency when they are used as gene delivery systems. of This review offers the stateof the art knowledge on the physiology and properties of EVs, namely, apoptotic vesicles, microvesiclesand exosomes as innovative drug delivery systems for gene therapy, with a special focus on targetingdendritic cells for the treatment of autoimmune disorders.