More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

Frey, Andreas; Lunding, Lars; Ehlers, Johanna Christine; Weckmann, Markus; Zissler, Ulrich M.; Wegmann, Michael

doi:10.3389/fimmu.2020.00761

Cited by 152 publications

(136 citation statements)

References 314 publications

(333 reference statements)

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“…Beneath the mucus barrier, the airway and alveolar epithelial cells themselves participate in the innate airway defense by forming a physical barrier against harmful external substances. 33 The epithelial layer accomplishes this selective permeability through the expression and regulation of multiple cell-cell adhesion complexes. [33][34][35] Tight junctions are composed of claudins and occludins and are most involved in preventing paracellular passage of luminal material.…”

Section: Epithelial Barriermentioning

confidence: 99%

“…33 The epithelial layer accomplishes this selective permeability through the expression and regulation of multiple cell-cell adhesion complexes. [33][34][35] Tight junctions are composed of claudins and occludins and are most involved in preventing paracellular passage of luminal material. Adherens junctions and desmosomes are involved in linking the actin cytoskeleton and intermediate filaments, respectively, on neighboring cells allowing the epithelium to remain intact.…”

Section: Epithelial Barriermentioning

confidence: 99%

See 1 more Smart Citation

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Michalski¹,

Schwartz²

2021

JIR

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Section: Epithelial Barriermentioning

confidence: 99%

Section: Epithelial Barriermentioning

confidence: 99%

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Michalski¹,

Schwartz²

2021

JIR

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“…Many cells (such as eosinophils, mast cells, T lymphocytes, neutrophils, and airway epithelial cells, etc.) and cellular elements participate in the pathogenesis of airway in ammation in asthma, in which T lymphocytes play a critical role [4][5][6][7][8] . Typically, it is known that T helper (Th)2 cells can secrete interleukins (IL-4, IL-5 and IL-13), and promote eosinophilic airway in ammation in atopic asthma [7][8][9] .…”

Section: Backgroudmentioning

confidence: 99%

Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

Wei

Liao

Jiang

et al. 2020

Preprint

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Background: The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.Methods: Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n=12) group, neutrophilic asthma (NA, n=10) group and paucigranulocytic asthma (PGA, n=6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n=10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.Results: The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.Conclusions: Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

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“…TJs are composed of the transmembrane proteins zona occludens-1 (ZO-1), occludin, claudins and junction adhesion molecules (JAMs) and are the main regulators of epithelial permeability [9]. The TJs of the zonula occludens and AJs of the zonula adherens constitute a dense protein network that prevents the paracellular passage of essentially all molecules including water, ions and proteins, as well as of pathogens or other inhaled particulate matter [10].…”

Section: Physical Barrier Functionmentioning

confidence: 99%

Airway epithelial cell damage in asthma: mechanisms and biomarkers

Yang

Jia

et al. 2020

Preprint

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Bronchial asthma is a heterogeneous disease with complex pathological mechanisms representing different phenotypes, including severe asthma. The airway epithelium is a major site of complex pathological changes in severe asthma due, in part, to activation of inflammatory and immune mechanisms in response to noxious agents. Current imaging procedures are unable to accurately measure epithelial and airway remodeling. Damage of airway epithelial cells occurs is linked to specific phenotypes and endotypes which provides an opportunity for the identification of biomarkers reflecting epithelial, and airway, remodeling. Identification of patients with more severe epithelial disruption using biomarkers may also provide personalized therapeutic opportunities and/or markers of successful therapeutic intervention. Here, we review the evidence for ongoing epithelial cell dysregulation in the pathogenesis of asthma, the sentinel role of the airway epithelium and how understanding these molecular mechanisms provides the basis for the identification of candidate biomarkers for asthma prediction, prevention, diagnosis, treatment and monitoring.

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More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

Cited by 152 publications

References 314 publications

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

Airway epithelial cell damage in asthma: mechanisms and biomarkers

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