T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles

Céspedes, Pablo F.; Jainarayanan, Ashwin Kumar; Fernández-Messina, Lola; Valvo, Salvatore; Saliba, David; Kurz, Elke; Kvalvaag, Audun; Chen, Lina; Ganskow, Charity S. G.; Colin‐York, Huw; Fritzsche, Marco; Peng, Yanchun; Dong, Tao; Johnson, Errin; Siller-Farfán, Jesús A.; Dushek, Omer; Sezgin, Erdinç; Peacock, Ben; Law, Alice Y.S.; Aubert, Dimitri; Engledow, Simon; Attar, Moustafa; Hester, Svenja; Fischer, Román; Sánchez‐Madrid, Francisco; Dustin, Michael L.

doi:10.1038/s41467-022-31160-3

Cited by 33 publications

(37 citation statements)

References 87 publications

(128 reference statements)

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“…Upon coating of 5μm silica beads with POPC:DGS-NTA(Ni) 98:2 mole percent of liposome solution, we verified proper bilayer formation by measuring diffusion of a fluorescent lipid analogue using fluorescence correlation spectroscopy (FCS) (fig. S1, A and B), which matched with previous data ( 5 , 6 ). We first generated fBSLBs carrying ACE2 and studied their interaction with SARS-CoV-2 spike expressing virus-like particles (+S-VLPs) using confocal microscopy (Fig.1, B and C).…”

Section: Resultssupporting

confidence: 88%

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A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens

Schlegel

Porębski

Andronico

et al. 2022

Preprint

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Speed is key during infectious disease outbreaks. It is essential, for example, to identify critical host binding factors to the pathogens as fast as possible. The complexity of host plasma membrane is often a limiting factor hindering fast and accurate determination of host binding factors as well as high-throughput screening for neutralizing antimicrobial drug targets. Here we describe MIGH-T, a multi-parametric and high-throughput platform tackling this bottleneck and enabling fast screens for host binding factors as well as new antiviral drug targets. The sensitivity and robustness of our platform was validated by blocking SARS-CoV-2 spike particles with nanobodies and IgGs from human serum samples.

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Section: Resultssupporting

confidence: 88%

“…fBSLBs were prepared similar as described previously ( 6 ). For preparation of one batch of fBSLBs, 1×10 7 5μm silica beads (Bangs Laboratories) were vortexed thoroughly and washed three times with PBS using 1500xg and 30 seconds centrifugation steps.…”

Section: Methodsmentioning

confidence: 99%

A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens

Schlegel

Porębski

Andronico

et al. 2022

Preprint

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“…Thus, TCR sorting and release in EVs was identified as a characteristic feature of the immune synapse 47 , 48 . Recent data showed that TCR signalling-induced T cell trans-synaptic vesicles contain greater levels of immune effectors (TCR, CD40L, RNA-binding proteins and miRNAs) than do constitutively released EVs 49 .…”

Section: Adaptive Immunitymentioning

confidence: 99%

The roles of extracellular vesicles in the immune system

2022

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The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.

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“…EVs are continuosly secreted from cells and it is well appreciated that they can modulate multiple aspects of the TME, where their function closely reflect the characteristics of their cell of origin [25,36,49]. Thus, it is relevant to point out that in our study, we found that only EVs released from activated CD4 + T cells were able to sensitize STING signaling in macrophages.…”

Section: Discussionmentioning

confidence: 51%

T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy

Hansen

Jensen

Ryttersgaard

et al. 2023

Preprint

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A key phenomenon in cancer is the establishment of a highly immunosuppressive tumor microenvironment (TME). Despite advances in immunotherapy, where the purpose is to induce tumor recognition and hence hereof tumor eradication, the majority of patients applicable for such treatment still fail to respond. It has been suggested that high immunological activity in the tumor is essential for achieving effective response to immunotherapy, which therefore have led to exploration of strategies that triggers inflammatory pathways. Here activation of the stimulator of interferon genes (STING) signaling pathway has been considered an attractive target, as it is a potent trigger of pro-inflammatory cytokines and type I and III interferons. However, immunotherapy combined with targeted STING agonists has not yielded sustained clinical remission in humans. This suggest a need for exploring novel adjuvants to improve the innate immunological efficacy. Here, we demonstrate that extracellular vesicles (EVs), derived from activated CD4+ T cells (T-EVs), sensitizes macrophages to elevate STING activation, mediated by IFN gamma carried on the T-EVs. Our work support that T-EVs can disrupt the immune suppressive environment in the tumor by reprogramming macrophages to a pro-inflammatory phenotype, and priming them for a robust immune response towards STING activation.

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T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles

Cited by 33 publications

References 87 publications

A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens

A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens

The roles of extracellular vesicles in the immune system

T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy

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