Qualitative differences in T‐cell activation by dendritic cell‐derived extracellular vesicle subtypes

Tkach, Mercedes; Kowal, Joanna; Zucchetti, Andrés E.; Enserink, Lotte; Jouve, Mabel; Lankar, Danielle; Saitakis, Michael; Martín-Jaular, Lorena; Théry, Clotilde

doi:10.15252/embj.201696003

Cited by 292 publications

(271 citation statements)

References 51 publications

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“…As an example of functional heterogeneity consider the release of EVs, rare when the cells are at rest, increased to a large extent, with an at least partially different composition, when the same cells are appropriately stimulated. Similar results, demonstrated in vivo in mice and humans, have also been reported in single cells grown in vitro , when their fluids are significantly changed [2,3,9,10].…”

Section: Extracellular Vesicles: Functions In General Cell Biology Ansupporting

confidence: 85%

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Meldolesi

2019

Clinical and Experimental Immunology

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Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression-inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re-expression of molecules from target cells.

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Section: Extracellular Vesicles: Functions In General Cell Biology Ansupporting

confidence: 85%

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Meldolesi

2019

Clinical and Experimental Immunology

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“…Furthermore, different EV subpopulations isolated from different fractions obtained by ultracentrifugation may have different biological functions. 45 Hence, the concept of EVs as biomarkers in NASH warrants careful validation in clinical studies.…”

Section: Lipotoxic Stress and Extrac Ellular Vesicle (Ev) Releasementioning

confidence: 99%

Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

Ibrahim

Hirsova

Gores

2018

Gut

218

197

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A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed nonalcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation.

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“…These exosomes, like their parent cells, are able to present allergens and stimulate T-cell responses by direct contact with CD4+ T cells or via the capture of these exosomes by other APCs [31, 32]. In this study, we found that TSLP activated DCs to release exosomes which can induce the production of Th2 cytokines such as IL-4 and promote Th2 differentiation.…”

Section: Discussionmentioning

confidence: 67%

Exosomes from Thymic Stromal Lymphopoietin-Activated Dendritic Cells Promote Th2 Differentiation through the OX40 Ligand

et al. 2018

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Objectives: Exosomes are extracellular vesicles released from various inflammatory cells, such as T cells, B cells, dendritic cells (DCs), and mast cells, which have been implicated in the modulation of immune response in asthma. This study aimed to investigate whether exosomes from DCs activated by thymic stromal lymphopoietin (TSLP) play a role in T-helper cell differentiation through the OX40 ligand (OX40L). Methods: Serum samples from patients with asthma were collected to measure the levels of OX40L, T-helper type 1 (Th1) cytokine interferon (IFN)-γ, and T-helper type 2 (Th2) cytokine interleukin (IL)-4 by enzyme-linked immunosorbent assay (ELISA). Exosomes were isolated from TSLP-activated DCs and co-cultured with CD4+ T cells. Western blot and ELISA assays were used to measure the levels of OX40L, IFN-γ, and IL-4 in DCs and CD4+ T cells. Flow cytometry was applied to detect Th1 and Th2 cells. Results: OX40L and IL-4 were increased and IFN-γ was decreased in serum from asthmatic patients compared with healthy controls. TSLP induced DCs to express OX40L in released exosomes, which could promote proliferation of CD4+ T cells, elevate the level of IL-4, and promote Th2 differentiation. Conclusion: Blockade of OX40L in DC-derived exosomes could inhibit exosome-mediated CD4+ T proliferation and Th2 differentiation.

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Qualitative differences in T‐cell activation by dendritic cell‐derived extracellular vesicle subtypes

Cited by 292 publications

References 51 publications

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

Exosomes from Thymic Stromal Lymphopoietin-Activated Dendritic Cells Promote Th2 Differentiation through the OX40 Ligand

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