Exosome secretion by eosinophils: A possible role in asthma pathogenesis

Mazzeo, Carla; Cañas, J. A.; Zafra, María Paz; Marco, Ainara Rojas; Fernández‐Nieto, Mar; Sanz, Verónica; Mittelbrunn, Marı́a; Izquierdo, Manuel; Baixaulli, Francesc; Sastre, Joaquı́n; Pozo, Victoria del

doi:10.1016/j.jaci.2014.11.026

Cited by 103 publications

(112 citation statements)

References 55 publications

(63 reference statements)

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“…Although MVBs were observed in the eosinophil cytoplasm during the present EM analyses, there was no ultrastructural evidence for exosome secretion. Our data are in part in accord with a work showing that stimulation of human eosinophils with CCL11 does not appear to increase secretion of CD63-positive exosomes (Mazzeo et al, 2015). On the other hand, these authors found that stimulation with interferon-gamma (INF-γ) induced exosome secretion by these cells (Mazzeo et al, 2015).…”

Section: Discussionsupporting

confidence: 93%

“…While the term exosomes is used for referring to a population of EVs, which are released from cells when multivesicular bodies (MVBs) fuse with the plasma membrane, the term MVs has been generally used for EVs formed by budding and shedding of the plasma membrane (reviewed in van der Pol et al, 2012; Twu and Johnson, 2014; Lawson et al, 2016). Recently, it was demonstrated that human eosinophils secrete exosomes in culture cell conditions and that this type of EV is increased in asthmatic patients, which links EVs with eosinophil activation (Mazzeo et al, 2015). However, the functions of EVs secreted by immune cells during inflammatory responses are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Microvesicle Production by Human Eosinophils Activated by “Inflammatory” Stimuli

Akuthota

Carmo

Bonjour

et al. 2016

Front. Cell Dev. Biol.

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A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking, and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs), very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1) and tumor necrosis factor alpha (TNF-α). EV production was investigated by nanoscale flow cytometry, conventional transmission electron microscopy (TEM) and pre-embedding immunonanogold EM. The tetraspanins CD63 and CD9 were used as EV biomarkers for both flow cytometry and ultrastructural immunolabeling. Nanoscale flow cytometry showed that human eosinophils produce EVs in culture and that a population of EVs expressed detectable CD9, while CD63 was not consistently detected. When eosinophils were stimulated immediately after isolation and analyzed by TEM, EVs were clearly identified as microvesicles (MVs) outwardly budding off the plasma membrane. Both CCL11 and TNF-α induced significant increases of MVs compared to unstimulated cells. TNF-α induced amplified release of MVs more than CCL11. Eosinophil MV diameters varied from 20 to 1000 nm. Immunonanogold EM revealed clear immunolabeling for CD63 and CD9 on eosinophil MVs, although not all MVs were labeled. Altogether, we identified, for the first time, that human eosinophils secrete MVs and that this production increases in response to inflammatory stimuli. This is important to understand the complex secretory activities of eosinophils underlying immune responses. The contribution of the eosinophil-derived MVs to the regulation of immune responses awaits further investigation.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Extracellular Microvesicle Production by Human Eosinophils Activated by “Inflammatory” Stimuli

Akuthota

Carmo

Bonjour

et al. 2016

Front. Cell Dev. Biol.

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“…In the last decade, potential pathological roles of exosomes in airway inflammation have been suggested by work showing the capacity of these vesicles to carry pro-inflammatory mediators (191,192). Moreover, eosinophils from asthmatic patients were recently shown to release increased amounts of exosomes (193). Thus, profiling the content of EMVs from all the body fluids discussed above using current 'omics' approaches may result in the identification of specific molecular signatures in vesicles from distinct populations of allergy and asthma patients.…”

Section: Exosomes and Microvesicles In Various Body Fluidsmentioning

confidence: 99%

Current and future biomarkers in allergic asthma

Zissler

Bieren

Jakwerth

et al. 2016

Allergy

102

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Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-typespecific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value.

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“…For example, mast cell-derived exosomes induce DCs to have an antigen-presenting capacity for T cells and modulate the activation of T lymphocytes to secrete cytokines such as IL-6, IL-12, and IFN-γ [23, 24]. Exosomes are also released by eosinophils and increased in asthmatic patients; they contain the main eosinophilic proteins and may play a role in driving the progression of asthma via eosinophils by increasing the production of chemokines, reactive oxygen species (ROS), and nitric oxide (NO) [25, 26]. B-cell-derived exosomes can specifically present antigens to T cells and induce T-cell responses [27].…”

Section: Discussionmentioning

confidence: 99%

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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Exosome secretion by eosinophils: A possible role in asthma pathogenesis

Cited by 103 publications

References 55 publications

Extracellular Microvesicle Production by Human Eosinophils Activated by “Inflammatory” Stimuli

Extracellular Microvesicle Production by Human Eosinophils Activated by “Inflammatory” Stimuli

Current and future biomarkers in allergic asthma

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

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