Decoy exosomes provide protection against bacterial toxins

Keller, Matthew D.; Ching, Krystal L; Liang, Feng; Dhabaria, Avantika; Tam, Kayan; Ueberheide, Beatrix; Unutmaz, Derya; Torres, Victor J.; Cadwell, Ken

doi:10.1038/s41586-020-2066-6

Cited by 184 publications

(163 citation statements)

References 30 publications

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“…Using a side scatter threshold and calibration beads ( Extended Data Fig. 3c ) 9, 10 , we successfully excluded aggregates and visualized PKH67 + TelC + telomere vesicles within ∼10% of the total APC single particle vesicle fraction ( Extended Data Fig. 3d ).…”

Section: Figurementioning

confidence: 99%

Intercellular telomere transfer extends T cell lifespan

Vaz

Vuotto

Valvo

et al. 2020

Preprint

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The common view is that T-lymphocytes activate telomerase, a DNA polymerase that extends telomeres at chromosome ends, to delay senescence. We show that independently of telomerase, T cells elongate telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs). Upon contact with T cells, APCs degraded shelterin to donate telomeres, which were cleaved by TZAP, and then transferred in extracellular vesicles (EVs) at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled them to fuse with T cell chromosomal ends causing an average lengthening of ∼3000 base pairs. Thus, we identify a previously unknown telomere transfer program that supports T cell lifespan.

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Section: Figurementioning

confidence: 99%

Intercellular telomere transfer extends T cell lifespan

Vaz

Vuotto

Valvo

et al. 2020

Preprint

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“…Since EVs have the same membrane orientation as the cells, they expose at their surface the extracellular domains of transmembrane proteins that can bind to short-distant or long-distant targets. By specifically binding to different proteins and protein-containing structures, EVs can act as a decoy for virus 7 and bacterial toxins 8 , thus having a potential role as therapeutic agents.…”

mentioning

confidence: 99%

Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus

Cocozza

Piovesana

Névo

et al. 2020

Preprint

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ABSTRACTSARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is 500 to 1500 times more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.

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“…Exos research has had its ups and downs. [ 34b,41 ] Initially, Exos were considered cell waste disposal bodies. [ 34b,41 ] However, later, the other important functions of Exos were identified, which assisted in understanding many hitherto unexplained biological paradoxes.…”

Section: Discussionmentioning

confidence: 99%

“…[ 34b,41 ] However, later, the other important functions of Exos were identified, which assisted in understanding many hitherto unexplained biological paradoxes. [ 34b,41 ] In this study, we isolated Exos (see Figure 6 A for reference) and incorporated Exos into our new hypothesis and proposed the “double stacking effect” hypothesis (Figure 3E)—a combination of the increase in the sensitivity/reactivity of vascular endothelial cells induced by Exos‐carrying EWSAT1 and the EWSAT1‐induced increase in angiogenic factor secretion from OS cells. Using in vitro and in vivo experiments, we verified the hypothesis and effectively targeted OS by designing precision drugs (EWSAT1‐KD) targeting EWSAT1.…”

Section: Discussionmentioning

confidence: 99%

EWSAT1 Acts in Concert with Exosomes in Osteosarcoma Progression and Tumor‐Induced Angiogenesis: The “Double Stacking Effect”

et al. 2020

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The prognosis for osteosarcoma (OS) continues to be unsatisfactory due to tumor recurrence as a result of metastasis and drug resistance. Several studies have shown that Ewing sarcoma associated transcript 1 (EWSAT1) plays an important role in the progression of OS. Exosomes (Exos) act as important carriers in intercellular communication and play an important role in the tumor microenvironment, especially in tumor‐induced angiogenesis. Nonetheless, the specific mechanism via which EWSAT1 and Exos regulate OS progression is unknown, and whether they can be effective therapeutic targets also requires verification. Hence, in this study, it is aimed to investigate the mechanisms of action of EWSAT1 and Exos. EWSAT1 significantly promotes proliferation, migration, colony formation, and survival of OS. EWSAT1 regulates OS‐induced angiogenesis via two mechanisms, called the “double stacking effect,” which is a combination of the increase in sensitivity/reactivity of vascular endothelial cells triggered by Exos‐carrying EWSAT1, and the EWSAT1‐induced increase in angiogenic factor secretion. In vivo experiments further validates the “double stacking effect” and shows that EWSAT1‐KD effectively inhibits tumor growth in OS. The above observations indicate that EWSAT1 can be used as not only a potential diagnostic and prognostic marker, but also as a precise therapeutic target for OS.

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Decoy exosomes provide protection against bacterial toxins

Cited by 184 publications

References 30 publications

Intercellular telomere transfer extends T cell lifespan

Intercellular telomere transfer extends T cell lifespan

Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus

EWSAT1 Acts in Concert with Exosomes in Osteosarcoma Progression and Tumor‐Induced Angiogenesis: The “Double Stacking Effect”

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