Dataset Information

Exosomes in Allergic Airway Diseases.

ABSTRACT: PURPOSE OF REVIEW:This review will cover what is known regarding exosomes and allergy, and furthermore discuss novel mechanism of exosome-mediated immune modulation and metabolic regulation via the transfer of mitochondria. RECENT FINDINGS:Exosomes are nano-sized extracellular vesicles (EVs) derived from the endosome that play a direct role in governing physiological and pathological conditions by transferring bioactive cargo such as proteins, enzymes, nucleic acids (miRNA, mRNA, DNA), and metabolites. Recent evidence suggest that exosomes may signal in autocrine but, most importantly, in paracrine and endocrine manner, being taken up by neighboring cells or carried to distant sites. Exosomes also mediate immunogenic responses, such as antigen presentation and inflammation. In asthma and allergy, exosomes facilitate cross-talk between immune and epithelial cells, and drive site-specific inflammation through the generation of pro-inflammatory mediators like leukotrienes. Recent studies suggest that myeloid cell-generated exosomes transfer mitochondria to lymphocytes. Exosomes are nano-sized mediators of the immune system which can modulate responses through antigen presentation, and the transfer of pro- and anti-inflammatory mediators. In addition to conventional mechanisms of immune modulation, exosomes may act as a novel courier of functional mitochondria that is capable of modulating the recipient cells bioenergetics, resulting in altered cellular responses. The transfer of mitochondria and modulation of bioenergetics may result in immune activation or dampening depending on the context.

SUBMITTER: Hough KP

PROVIDER: S-EPMC7117871 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Exosomes in Allergic Airway Diseases.

Hough K P KP Deshane J S JS

Current allergy and asthma reports 20190322 5

<h4>Purpose of review</h4>This review will cover what is known regarding exosomes and allergy, and furthermore discuss novel mechanism of exosome-mediated immune modulation and metabolic regulation via the transfer of mitochondria.<h4>Recent findings</h4>Exosomes are nano-sized extracellular vesicles (EVs) derived from the endosome that play a direct role in governing physiological and pathological conditions by transferring bioactive cargo such as proteins, enzymes, nucleic acids (miRNA, mRNA, ...[more]

PMID: 30903454

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Project description:BackgroundSignifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation.ObjectiveWe sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers.MethodsAdults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified.ResultsHDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models.ConclusionsRepetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Project description:PurposeBacterial extracellular vesicles (EVs) play crucial roles in bacteria-host interactions. Due to their cargo, EVs are considered fingerprints of the parent cell, which are detectable in body fluids. We studied the composition and function of bacterial microbiota-derived EVs genes in urine to evaluate whether they have specific characteristics concerning allergic airway disease.MethodsSubjects were from elementary school surveys and classified into 3 groups according to questionnaires and sensitization to aeroallergens: the allergic airway group (AA, n = 16), atopic controls (AC, n = 7) and healthy controls (HC, n = 26). The bacterial EVs were isolated from voided urine samples, their nucleic acid was extracted for 16S ribosomal RNA pyrosequencing and then characterized using α-diversity, β-diversity, network analysis, intergroup comparison of bacterial composition and predicted functions, and correlation with total immunoglobulin E (IgE), eosinophils% and fractional exhaled NO.ResultsThe compositional α-diversity was the highest in AA, while functional α-diversity was the highest in HC. AA had a distinct clustering with the least intersample variation. Klebsiella, Haemophilus, members from Lachnospiraceae and Ruminococcaceae, and the pathways of sphingolipid and glycerolipid metabolism, and biosynthesis of peptidoglycan and lysine were the highest in AA and positively correlated with total IgE or eosinophil%. Genetic information processing function contributed to 48% of the intergroup variance and was the highest in AA. Diaphorobacter, Acinetobacter, and the pathways of short-chain fatty acids and anti-oxidants metabolism, lysine and xenobiotic degradation, and lipopolysaccharide biosynthesis were the lowest in AA and negatively correlated with total IgE or eosinophil%. The bacterial composition and function in AC were closer to those in HC. The bacterial network was remarkably dense in HC.ConclusionsThe bacterial microbiota-derived EVs in urine possess characteristic features in allergic airway disease with a remarkable correlation with total IgE and eosinophil%. These findings suggest that they may play important roles in allergic airway diseases.

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Exosomes in Allergic Airway Diseases.

Publications

Exosomes in Allergic Airway Diseases.

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