Extracellular vesicles: important players in immune homeostasis

Isola, Allison L.; Chen, Suzie

doi:10.21037/atm.2017.03.76

Cited by 11 publications

(11 citation statements)

References 6 publications

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“…EVs participate in intercellular communication and are integral components of the ECM (24,(27)(28)(29)(30)(31). They have been shown to mediate matrix remodeling, tissue injury repair, and tumor invasion through promotion of cell migration as well as ECM degradation (3,4,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Fibronectin on the Surface of Extracellular Vesicles Mediates Fibroblast Invasion

Chanda

Otoupalova²,

Hough

et al. 2019

Am J Respir Cell Mol Biol

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Extracellular vesicles (EVs) are endosome and plasma membrane-derived nano-sized vesicles that participate in intercellular signaling. Although EV cargo may signal via multiple mechanisms, how signaling components on the surface of EVs mediate cellular signaling is less well understood. In this study, we show that fibroblast-derived EVs carry fibronectin on the vesicular surface, as evidenced by mass spectrometry-based proteomics (Sequential Window Acquisition of all Theoretical Mass Spectra) and flow-cytometric analyses. Fibroblasts undergoing replicative senescence or transforming growth factor b1-induced senescence and fibroblasts isolated from human subjects with an agerelated lung disorder, idiopathic pulmonary fibrosis, secreted higher numbers of EVs than their respective controls. Fibroblast-derived EVs induced an invasive phenotype in recipient fibroblasts. This invasive fibroblast phenotype was dependent on EV surface localization of fibronectin, interaction with the fibronectin receptor a5b1 integrin, and activation of invasion-associated signaling pathways involving focal adhesion kinase and Src family kinases. EVs in the cellular supernatant, unbound to the extracellular matrix, were capable of mediating invasion signaling on recipient fibroblasts, supporting a direct interaction of EV surface fibronectin with the plasma membrane of recipient cells. Together, these studies uncover a novel mechanism of EV signaling of fibroblast invasion that may be relevant in the pathogenesis of fibrotic diseases and cancer.

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Section: Discussionmentioning

confidence: 99%

Fibronectin on the Surface of Extracellular Vesicles Mediates Fibroblast Invasion

Chanda

Otoupalova²,

Hough

et al. 2019

Am J Respir Cell Mol Biol

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“…All types of EVs, in addition to their increasingly recognised roles in pathogenesis, play important roles in homeostasis. One of the first direct demonstrations of a physiological role for MVs was provided by elegant works from Denisa Wagner's team, indicating that platelet MVs are crucial in initiating clot formation [56]; the multiple physiological roles of exosomes, notably in immune homeostasis have been reviewed recently [57]. Another area in which EVs are likely to play important homeostatic roles is pregnancy.…”

Section: Evs In Homeostasismentioning

confidence: 99%

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

Macia

Nanan

Hosseini‐Beheshti

et al. 2019

IJMS

165

141

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Extracellular vesicles (EVs) are blebs of either plasma membrane or intracellular membranes carrying a cargo of proteins, nucleic acids, and lipids. EVs are produced by eukaryotic cells both under physiological and pathological conditions. Genetic and environmental factors (diet, stress, etc.) affecting EV cargo, regulating EV release, and consequences on immunity will be covered. EVs are found in virtually all body fluids such as plasma, saliva, amniotic fluid, and breast milk, suggesting key roles in immune development and function at different life stages from in utero to aging. These will be reviewed here. Under pathological conditions, plasma EV levels are increased and exacerbate immune activation and inflammatory reaction. Sources of EV, cells targeted, and consequences on immune function and disease development will be discussed. Both pathogenic and commensal bacteria release EV, which are classified as outer membrane vesicles when released by Gram-negative bacteria or as membrane vesicles when released by Gram-positive bacteria. Bacteria derived EVs can affect host immunity with pathogenic bacteria derived EVs having pro-inflammatory effects of host immune cells while probiotic derived EVs mostly shape the immune response towards tolerance.

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“…The release of biological signals within phospholipid-bound membranes could have originated as a method of eliminating damaged cellular components, and subsequently, may have provided a warning to local and distant cells acting as a primitive immune system (van Niel et al, 2018;Margolis and Sadovsky, 2019;Correa et al, 2020). EVs are now known to be critical mediators of intercellular communication and even act on the immune system and immune cells (Robbins and Morelli, 2014;Isola and Chen, 2017). Their cargo consists of antigens, cytokines, membrane proteins, microRNAs, and long/short noncoding RNAs.…”

Section: Nsc-evs and Immune Responsesmentioning

confidence: 99%

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Willis

Nicaise

Hamel

et al. 2020

Front. Cell. Neurosci.

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Increasing evidence foresees the secretome of neural stem cells (NSCs) to confer superimposable beneficial properties as exogenous NSC transplants in experimental treatments of traumas and diseases of the central nervous system (CNS). Naturally produced secretome biologics include membrane-free signaling molecules and extracellular membrane vesicles (EVs) capable of regulating broad functional responses. The development of high-throughput screening pipelines for the identification and validation of NSC secretome targets is still in early development. Encouraging results from pre-clinical animal models of disease have highlighted secretome-based (acellular) therapeutics as providing significant improvements in biochemical and behavioral measurements. Most of these responses are being hypothesized to be the result of modulating and promoting the restoration of key inflammatory and regenerative programs in the CNS. Here, we will review the most recent findings regarding the identification of NSC-secreted factors capable of modulating the immune response to promote the regeneration of the CNS in animal models of CNS trauma and inflammatory disease and discuss the increased interest to refine the pro-regenerative features of the NSC secretome into a clinically available therapy in the emerging field of Regenerative Neuroimmunology.

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Extracellular vesicles: important players in immune homeostasis

Cited by 11 publications

References 6 publications

Fibronectin on the Surface of Extracellular Vesicles Mediates Fibroblast Invasion

Fibronectin on the Surface of Extracellular Vesicles Mediates Fibroblast Invasion

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

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