![]() Conversely, EVs derived from cells such as mesenchymal stem cells and anti-inflammatory immune cells produce EVs that promote cellular health with the potential to resolve inflammatory injury and cell stress ( 27– 33). Deleterious actions can reflect disease states and/or drive disease pathology such as disease-associated misfolded proteins, dysfunctional mitochondria, oxidative stressors, pro-inflammatory immune signaling components, and signaling promoting cellular injury and death ( 5, 20– 26). EV distribution and communication among cells in an organism is both local and systemic.ĮV functions can be deleterious or beneficial. Uptake and delivery of these EV packages and their cargo are accomplished through multiple recipient cell mechanisms such as membrane fusion, endocytosis, ligand-receptor interactions, antigen presentation, phagocytosis, macropinocytosis, lipid-raft, and more ( 17– 19). Larger apoptotic bodies (~1-5 microns in size) are formed during the late stages of apoptosis as part of cell shrinkage and associated programmed cell death ( 12– 16). Micro/nanovesicle populations (~50-1000nm) result from the outward budding and fission of the plasma membrane. Specifically, exosomes (~20-200nm) are packaged and generated through the endosomal pathway via fusion of multivesicular bodies with the plasma membrane. These EV signaling packages can be further delineated by their size as well as their biogenesis. EVs use signaling proteins, enzymes, coding and non-coding RNA (mRNA, microRNA, long noncoding RNA, etc.), DNA, surface proteins and receptors, lipids, and glycoproteins for intercellular signaling ( 9– 11). EVs are membrane-encapsulated particles ranging from approximately 20 nm to 1000nm and are released by cells into the extracellular space. ![]() These packages are now studied for their ability to modify cellular processes in health and disease ( 5– 8). However, additional evidence suggests that EVs can participate in active intercellular communication via transmission of signaling cargo ( 3, 4). ![]() These findings support the therapeutic potential of expanded Treg EVs to suppress pro-inflammatory responses in human disease.Įxtracellular vesicles (EVs) were originally proposed as a mechanism for cells to dispose of damaged organelles, proteins, and nucleic acids ( 1, 2). In a mouse model of amyotrophic lateral sclerosis, intranasal administration of enriched Treg EVs slowed disease progression, increased survival, and modulated inflammation within the diseased spinal cord. Intranasal administration of enriched Treg EVs in this model also reduced pro-inflammatory transcripts and the associated neuroinflammatory responses. Intravenous injection of Treg EVs into an LPS-induced mouse model of inflammation reduced peripheral pro-inflammatory transcripts and increased anti-inflammatory transcripts in myeloid cells as well as Tregs. The present study demonstrates that ex vivo expanded Tregs generate a large pool of EVs that express Treg-associated markers and suppress pro-inflammatory responses in vitro and in vivo. Cell-based immune therapies, including regulatory T cells (Tregs), are currently being clinically evaluated for their usefulness in suppressing pro-inflammatory processes. Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, United StatesĮxtracellular vehicles (EVs) are efficient biomarkers of disease and participate in disease pathogenesis however, their use as clinical therapies to modify disease outcomes remains to be determined. ![]() Thonhoff, Weihua Zhao, Alireza Faridar, Jinghong Wang, David R.
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