An Updated View of the Importance of Vesicular Trafficking and Transport and Their Role in Immune-Mediated Diseases: Potential Therapeutic Interventions

Abstract

Cellular trafficking is the set of processes of distributing different macromolecules by the cell. This process is highly regulated in cells, involving a system of organelles (endomembranous system), among which are a great variety of vesicles that can be secreted from the cell, giving rise to different types of extracellular vesicles (EVs) that can be captured by other cells to modulate their function. The cells of the immune system are especially sensitive to this cellular traffic, producing and releasing different classes of EVs, especially in disease states. There is growing interest in this field due to the therapeutic and translational possibilities it offers. Different ways of taking advantage of the understanding of cell trafficking and EVs are being investigated, and their use as biomarkers or therapeutic targets is being investigated. The objective of this review is to collect the latest results and knowledge in this area with a specific focus on immune-mediated diseases. Although some promising results have been obtained, further knowledge is still needed, at both the basic and translational levels, to understand and modulate cellular traffic and EVs for better clinical management of these patients.

Induction of Vesicular Trafficking and JNK-Mediated Apoptotic Signaling in Mononuclear Leukocytes Marks the Immuno-Proteostasis Response to Uremic Proteins

“…7). Regardless of the endocytosis mechanism (recently reviewed in [46]), the fact that uremic material from the external milieu can mobilize to mononuclear leukocytes implies the activation of retrograde transport mechanisms by the vesicular system of these cells. This is a para-physiological process that can contribute to systemic proteostasis [47,48] involving molecular chaperones [49] active in capturing unfolded or misfolded proteins in the ex-tracellular compartments and leading them to intracellular proteostasis modules, essentially the ER for protein repair or lysosomes and autophagosomes for proteolysis and removal/recycling [50].…”

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…Recent updates unravel the crucial role of EVs and vesicular trafficking in the immune system ( 65 ) and during the pathogenesis of immune-based diseases, in addition to their therapeutic perspectives ( 218 ). An accurate understanding of the mechanisms by which tumors or other pathological statuses induce immune cell dysfunction via their extracellular particles will allow a better understanding of how vesicles interact with the cells of the immune system.…”

Unfolding the role of placental-derived Extracellular Vesicles in Pregnancy: From homeostasis to pathophysiology

“…Then, the late endosomes can either fuse with lysosomes and be degraded or they can move to the plasma membrane. After fusion of the MVB with the cell membrane, the ILVs are released to the extracellular space, being designed as exosomes ( Ortega et al, 2022a ). Microvesicles are formed by direct budding of the plasma membrane, as a result of coordinated work between membrane phospholipids and the contractile action of the cellular cytoskeleton ( Kalra et al, 2016 ).…”

“…Apoptotic bodies are phagocytosed by different cells, especially macrophages in the process of spherocytosis ( Kourtzelis et al, 2020 ). Once the EVs enter in the recipient cell, they can be recycled back to the plasma membrane and released, or they can be directed to MVBs, where they will fuse with lysosomes for degradation or their content will be released in the cytosol, nucleus, or ER, where they will exert their cellular functions ( Ortega et al, 2022a ).…”