T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles

Ax, Elisabeth; Jevnikar, Zala; Cvjetkovic, Aleksander; Malmhäll, Carina; Olsson, Henric; Rådinger, Madeleine; Lässer, Cecilia

doi:10.1186/s12931-020-01402-3

Cited by 21 publications

(16 citation statements)

References 51 publications

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“…Protein enrichment analysis with reference to Gene Ontology (GO) "Cellular Component" sub-domain revealed that the PEx matrix is enriched in extracellular proteins associated with "exosome" (Figure 3, Table 2A). This nding is particularly interesting due to the emerging role of the exosomes as mediators of biomarkers for several chronic lung diseases [29,30]. In addition, based on results from the GO "Biological Processes" domain analysis, PEx proteome seem highly relevant for studies on the role of innate immune response in development of respiratory diseases and host defence.…”

Section: Discussionmentioning

confidence: 99%

A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

Östling¹,

Geest

Olsson

et al. 2020

Preprint

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BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway dysfunction (SAD), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with SAD as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with small airway dysfunction. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

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Section: Discussionmentioning

confidence: 99%

A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

Östling¹,

Geest

Olsson

et al. 2020

Preprint

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“…Structural lung cells, including airway epithelial cells (AECs) and airway smooth muscle cells (ASMCs), play pivotal roles in asthmatic disease and inflammation [ 207 , 208 ]. T2 cytokine-stimulated exosomes presented an increase in nitric oxide synthase 2 (NOS2), and exosomes from T17-stimulated epithelial cells showed a capacity for neutrophil chemotaxis.…”

Section: Exosomes From Other Cellular Populations Implicated In Asmentioning

confidence: 99%

Exosomes: A Key Piece in Asthmatic Inflammation

Cañas

Rodrigo‐Muñoz

Gil-Martínez

et al. 2021

IJMS

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Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.

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“…Several studies by Woodruff and colleagues have demonstrated the ability of the airway epithelium to respond with unique gene and protein signatures in response to T2 cytokines, and that these signatures could be used as biomarkers for T2 asthma [ 177 , 178 , 179 ]. One of the proteins from this T2 signature is periostin, which is increased in epithelial cells in response to IL-13 +/− IL-4 [ 177 , 180 , 181 ], and which may have potential as a systemic biomarker of eosinophilic airway inflammation [ 182 , 183 ]. Periostin, a matricellular protein, has been implicated in processes related to airway remodeling such as cell proliferation, collagen production and epithelial-to-mesenchymal transition [ 184 ], as well as subepithelial fibrosis [ 185 ], mainly driven by TGF-β activation.…”

Section: The Effect Of T2 Inflammation On the Airway Epitheliummentioning

confidence: 99%

“…Higher levels of nitric oxide are usually linked to increased levels of inducible nitric oxide synthase (NOS2) in the airway epithelium, which can be normalized through the administration of corticosteroids [ 208 , 209 , 210 ]. Several cytokines can increase the levels of NOS2 on both the gene and protein level [ 208 , 210 ], though the effect is suggested to be stronger from T2 cytokines including IL-4 and IL-13 [ 181 , 211 ].…”

Section: The Effect Of T2 Inflammation On the Airway Epitheliummentioning

confidence: 99%

“…Of these, CCL26 has been shown to be the strongest inducer of eosinophil migration in asthmatic individuals [ 212 ]. Several studies have shown that this chemokine is strongly induced by IL-13 in airway epithelial cells ( Figure 3 ) [ 181 , 207 , 213 , 214 ] and further that it is elevated in serum and bronchial biopsies from asthmatic individuals [ 183 , 207 ] and correlates with sputum eosinophil counts [ 213 ]. Recently, interest has grown when it comes to the involvement of extracellular vesicles, or exosomes, in asthma pathology and their potential as biomarkers.…”

Section: The Effect Of T2 Inflammation On the Airway Epitheliummentioning

confidence: 99%

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The Airway Epithelium—A Central Player in Asthma Pathogenesis

Calvén

Rådinger

2020

IJMS

Self Cite

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Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction in response to a wide range of exogenous stimuli. The airway epithelium is the first line of defense and plays an important role in initiating host defense and controlling immune responses. Indeed, increasing evidence indicates a range of abnormalities in various aspects of epithelial barrier function in asthma. A central part of this impairment is a disruption of the airway epithelial layer, allowing inhaled substances to pass more easily into the submucosa where they may interact with immune cells. Furthermore, many of the identified susceptibility genes for asthma are expressed in the airway epithelium. This review focuses on the biology of the airway epithelium in health and its pathobiology in asthma. We will specifically discuss external triggers such as allergens, viruses and alarmins and the effect of type 2 inflammatory responses on airway epithelial function in asthma. We will also discuss epigenetic mechanisms responding to external stimuli on the level of transcriptional and posttranscriptional regulation of gene expression, as well the airway epithelium as a potential treatment target in asthma.

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T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles

Cited by 21 publications

References 51 publications

A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

Exosomes: A Key Piece in Asthmatic Inflammation

The Airway Epithelium—A Central Player in Asthma Pathogenesis

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