Vesicular trafficking in immune regulation and disease: from intracellular sorting to intercellular communication

Abstract

Vesicular trafficking is a fundamental mechanism that maintains cellular homeostasis, enables precise material transport, and regulates signal transduction in eukaryotic cells. In immune cells, vesicular trafficking supports dynamic membrane remodeling and activation-dependent vesicle release, while the biological effects of vesicle-associated signals are shaped by cargo composition, cellular origin, and the surrounding immunological context. These features support rapid and context-dependent responses to pathogens, tissue damage, and tumors. Immune cells both generate vesicular outputs and respond to trafficking-dependent changes in receptor localization, cargo composition, and extracellular vesicle signals. This close dependence on trafficking makes immune functions particularly vulnerable to perturbations in the underlying network. This review summarizes the roles of vesicular trafficking in immune regulation and disease. We first outline the specialized features of trafficking in immune cells and their sensitivity to perturbations. We then highlight its key functions in antigen processing and presentation, directional secretion at the immunological synapse, T cell receptor and B cell receptor trafficking, and the spatiotemporal control of inflammatory signaling via compartmentalized endosomal and lysosomal pathways. Finally, we discuss how trafficking defects contribute to immunodeficiency, autoimmunity, chronic inflammation, and tumor immune evasion, and briefly consider emerging therapeutic strategies that target trafficking pathways and extracellular vesicle-based platforms. By linking intracellular sorting decisions with intercellular communication, vesicular trafficking provides a unifying framework for understanding immune regulation and immune-mediated disease.