The Role of Airway Epithelial Cell Alarmins in Asthma

Whetstone, Christiane E.; Ranjbar, Maral; Omer, Hafsa; Cusack, Ruth; Gauvreau, Gail M.

doi:10.3390/cells11071105

Cited by 28 publications

(31 citation statements)

References 258 publications

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“…In another study on patients with mild atopic asthma, the epithelium and submucosa of bronchial biopsies showed increased immunoreactivity to IL-25, IL-33, and TSLP after allergen challenge (72). These findings highlight the role of airway epithelial cells in supporting inflammation by synthesizing lipid mediators and cytokines, which contribute to some of the pathological features of asthma (1,73). As part of the initial steps in allergic response to inhaled particles and pathogens, the airway epithelial cells release chemokines and cytokines to attract and activate dendritic cells.…”

Section: Epithelial Cells In Asthmamentioning

confidence: 89%

Role of airway epithelial cell miRNAs in asthma

et al. 2022

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The airway epithelial cells and overlying layer of mucus are the first point of contact for particles entering the lung. The severity of environmental contributions to pulmonary disease initiation, progression, and exacerbation is largely determined by engagement with the airway epithelium. Despite the cellular cross-talk and cargo exchange in the microenvironment, epithelial cells produce miRNAs associated with the regulation of airway features in asthma. In line with this, there is evidence indicating miRNA alterations related to their multifunctional regulation of asthma features in the conducting airways. In this review, we discuss the cellular components and functions of the airway epithelium in asthma, miRNAs derived from epithelial cells in disease pathogenesis, and the cellular exchange of miRNA-bearing cargo in the airways.

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Section: Epithelial Cells In Asthmamentioning

confidence: 89%

Role of airway epithelial cell miRNAs in asthma

et al. 2022

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“…We also studied epithelial-cell-derived IL-33, IL-25, and TSLP, which were regarded as alarmins and played pivotal roles in the initiation of allergic inflammation in asthma ( 29 ). Their receptors widely expressed in structural cells and innate and adaptive immune cells, contributing to the airway disease by driving inflammatory processes ( 30 ). The expression of IL-33, IL-25, and TSLP should be higher in ABPA and asthma theoretically.…”

Section: Discussionmentioning

confidence: 99%

Clinical and immunological characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis

Chen

Zhang

et al. 2022

Front. Immunol.

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BackgroundAspergillus fumigatus (A.f) is a common airborne allergen that contributes to allergic asthma. In some patients, A.f can colonize in the airway and lead to allergic bronchopulmonary aspergillosis (ABPA). However, our understanding of the pathogenesis of A.f-sensitized asthma and ABPA remains inadequate.ObjectiveWe aimed to investigate the clinical and immunological characteristics of A.f-sensitized asthma and ABPA.MethodsA total of 64 ABPA and 57 A.f-sensitized asthma patients were enrolled in the study, and 33 non-A.f-sensitized asthma patients served as the control group. The clinical and immunological parameters included lung function, fractional exhaled nitric oxide (FeNO), induced sputum and blood cell analysis, specific IgE/IgG/IgA of A.f and its components, cytokines (IL-33, IL-25, and TSLP) and CD4+T cell subsets.ResultsThe eosinophils in blood, induced sputum, and FeNO were significantly higher in ABPA patients compared to that in A.f-sensitized patients. The combination of FeNO and eosinophils (EO) parameters presented good diagnostic efficiency in differentiating A.f (+) asthma from ABPA, with a sensitivity of 80% and a specificity of 100%. Specific IgE, IgG, and IgA against A.f also increased in ABPA patients. However, serum IL-25, IL-33, and TSLP showed no significant differences between the two groups. Cell analysis showed an increase in IFN-γ+Th1 cells in the ABPA patients. FlowSOM analysis further confirmed that the frequency of CD3+CD4+PD-1+CD127+IFN-γ+T cells was higher in ABPA patients.ConclusionOur findings suggest the distinct humoral and cell immunological responses in A.f-sensitized asthma and ABPA patients. ABPA patients have more severe eosinophilic inflammation and enhanced Th1 responses compared with A.f-sensitized asthma patients.

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“…IL-25 directly enhances Th2 cytokine production from Th2 memory cells activated by TSLP. IL-25 M a n u s c r i p t a c c e p t e d f o r p u b l i c a t i o n release by airway epithelial cells contributes to many pathogenic features of asthma, including the recruitment of eosinophils, airway mucus over secretion, and airway remodeling (29).…”

Section: The Role Of Airway Epithelium In Asthmamentioning

confidence: 99%

“…IL-33 is one of the earliest cytokines released in response to allergens and is central in the activation of both the innate and adaptive immune response (30). IL-33 has been shown to be responsible for inducing early immune development and polarization toward type 2 T cell inflammation through two mechanisms: activating the maturation of resident dendritic DC and inducing DC-stimulated differentiation of naïve CD4 + T cells into polarized Th2 cells (29). IL-33 levels are elevated in the lung epithelium, airway smooth muscle, and bronchoalveolar lavage, correlating with disease severity.…”

Section: The Role Of Airway Epithelium In Asthmamentioning

confidence: 99%

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From triggers to asthma: a narrative review on epithelium dysfunction

Cecchi¹,

Vaghi²,

Bini³

et al. 2022

Eur Ann Allergy Clin Immunol

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It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

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The Role of Airway Epithelial Cell Alarmins in Asthma

Cited by 28 publications

References 258 publications

Role of airway epithelial cell miRNAs in asthma

Role of airway epithelial cell miRNAs in asthma

Clinical and immunological characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis

From triggers to asthma: a narrative review on epithelium dysfunction

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