Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Laulajainen‐Hongisto, Anu; Toppila‐Salmi, Sanna; Luukkainen, Annika; Kern, Robert C.

doi:10.3389/fcell.2020.00204

Cited by 23 publications

(20 citation statements)

References 210 publications

(268 reference statements)

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“…Although host factors that make asthma subjects susceptible to airway structural changes are complex and poorly understood, multiple studies support the concept of airway epithelial barrier dysfunction as being critical for this process [1,5]. The airway epithelium is continuously exposed to airborne particles and infectious agents and represents the airways' frontline barrier between the host and environment.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it plays a vital role in the innate immune defense and mucociliary clearance. As a source of cytokines and growth factors, the airway epithelium regulates other cell functions [5,6]; for example, it stimulates lung fibroblasts to produce ECM components, such as collagens and fibronectin, and pro-fibrotic transforming growth factor (TGF)-β [1]. Moreover, known environmental risk factors, such as cigarette smoke, biomass fuel particles, and respiratory viral infections, may stimulate the production of ECM proteins by the airway epithelium, fibroblasts, and smooth muscle cells [1].…”

Section: Introductionmentioning

confidence: 99%

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Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients

Bazan-Socha

Buregwa-Czuma

Jakieła

et al. 2021

IJMS

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Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients

Bazan-Socha

Buregwa-Czuma

Jakieła

et al. 2021

IJMS

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“…Asthma, CRS, and AR are all multifactorial chronic airway diseases that have partly overlapping pathogenetic mechanisms and risk factors [ 24 ]. These environmental risk factors, such as exposure to pollution and tobacco smoke, are linked to asthma and CRS pathogenesis and disease aggravation via the disruption of interplay of epithelial barriers with particles, allergens, and microbes [ 25 , 26 ]. In CRS, the most commonly discussed microbial agent is Staphylococcus aureus , but some evidence also implicates dysbiosis of the microbial community as a whole rather than a specific dominant pathogen [ 5 , 27 ].…”

Section: Chronic Inflammatory Airway Diseasesmentioning

confidence: 99%

“…In AR, there is evidence that the sensitization profile and/or allergic multimorbidity are associated with morbidity in children [ 28 ] and adults [ 29 ]. In asthma, differences are seen between different asthma types in their genetic backgrounds, association with AR and CRS, and possibly also in microbe–host interactions [ 26 ]. Childhood-onset asthma is, more often than adult-onset asthma, associated with genetic predisposition, whereas the background of adult-onset asthma is often multifactorial.…”

Section: Chronic Inflammatory Airway Diseasesmentioning

confidence: 99%

Monoclonal Antibodies and Airway Diseases

Lyly

Laulajainen‐Hongisto

Gevaert

et al. 2020

IJMS

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Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.

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“…Many of the environmental risk factors in the pathogenesis of asthma and CRS are linked to disrupted interplay between epithelial barriers, particles, allergens and microbes [8, 9 ]. Type 2 biased inflammation with recruitment of eosinophils, basophils, and T‐cells, and release of cytokines is common in atopic asthma and AR [10, 11 ].…”

Section: Introductionmentioning

confidence: 99%

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

Laulajainen‐Hongisto

Lyly

Hanif

et al. 2020

Clin Transl Allergy

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Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10–8) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR–associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.

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Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Cited by 23 publications

References 210 publications

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients

Monoclonal Antibodies and Airway Diseases

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

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