About this Research Topic
The release of small membrane-bound vesicles into the extracellular environment is a widespread phenomenon in biological systems. Nanoscale vesicles (~30-200 nm in diameter) are released by cells of the mammalian immune, cardiovascular and nervous systems, from cancer cells and microbes, and are co-opted in the production of some enveloped viruses. The release of microvesicles by numerous cell-types and in diverse organisms suggests their involvement in important, evolutionarily conserved, cellular and systemic functions. Despite, or perhaps because of, their ubiquity and diversity, a detailed mechanistic understanding of extracellular microvesicle (EMV) biogenesis and function remains enigmatic. One well-studied route of EMV production is through multivesicular body (MVB) exocytosis, in which, fusion of the limiting membrane of MVBs with the cell plasma membrane results in release of their intraluminal vesicles (ILVs) – typically called exosomes. It is clear that the ESCRT (endosomal sorting complexes required for transport) pathway and Rab GTPases are central to MVB (and exosome) biogenesis and cargo selection. However, EMVs can also arise by direct budding from the cell’s plasma membrane (sometimes called ectosomes), a process that is topologically equivalent to ILV production in MVBs, and utilizes similar cellular machinery. The lack of unique or universal markers that differentiate exosomes and ectosomes has hampered their detailed characterization. Production of microvesicles from either subcellular compartment can also occur through ESCRT-independent mechanisms, such as by membrane lipid reorganization that promotes membrane vesiculation. Importantly, enveloped viruses like HIV can exploit host-cell budding machinery, and selectively incorporate host cell components, for cell-cell transmission at ‘virological synapses’.
Recent reports of EMV production, polarized release, and uptake by immune cells, has spurred interest in (re)examining their role in intercellular communication and effector functions in immune responses. The release of EMVs from lymphocytes and dendritic cells is frequently observed, and their uptake across immunological synapses by recipient immune cells has recently been shown to modulate cellular functions. Similarly, production and transfer of bioactive EMVs have been reported in mast cells, macrophages and dendritic cells, and EMVs produced by tumor cells have been implicated in cancer-related immunosuppression of tumor-infiltrating lymphocytes and tumor-associated myeloid cells.
We were motivated to establish this Frontiers Research Topic to organize recent findings and current perspectives on EMV biogenesis and function in the immune system. We welcome contributions from investigators across biological disciplines (including immunology, immunopathology, virology, cell and membrane biology), whose recent work lends insight into EMV production, function and regulation in physiological and aberrant immune responses. A key goal of this Topic is to emphasize the subcellular mechanisms and governing principles involved. We encourage contributors to place their work within a broader cell-biological or systems context, discuss unifying and divergent principles, and speculate on future directions and priorities of this fast-emerging field.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.