Chronic inflammatory airway diseases: the central role of the epithelium revisited

Gohy, Sophie; Hupin, Cloé; Pilette, Charles; Ladjemi, Maha Zohra

doi:10.1111/cea.12712

Cited by 72 publications

(73 citation statements)

References 178 publications

(210 reference statements)

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“…Over time, retained sputum can cause mucous plugs and airway obstruction, obliteration, and damage resulting in more advanced bronchiectasis (6,7). These structural abnormalities in small airways allow for mucus stasis, which favors continued chronic infection and the persisted vicious cycle in patient with bronchiectasis (8,24).…”

Section: Discussionmentioning

confidence: 99%

“…In non-CF bronchiectasis, the epithelium is damaged and has increased susceptibility to injury as compared to normal airway epithelium. Failure of appropriate growth and differentiation of epithelial cells causes persistent mucosal injury (8). Ciliary dyskinesia and mucus over-production weakens clearance of respiratory pathogens from the airway (7).…”

Section: Introductionmentioning

confidence: 99%

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Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) μm, P<0.0001; bronchioles: 7.46 (6.41-8.48) μm, P<0.0001] as compared to nonhyperplastic epithelium (bronchi: 5.60 μm; bronchioles: 4.89 μm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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“…Besides its role as a selective and highly regulated physical barrier through the establishment of the intercellular apical junctional complexes between neighbouring airway epithelial cells (AECs) [8][9][10][11], airway epithelium also acts as a critical orchestrator of the airway immune response through the secretion of a wide repertoire of molecules, including antimicrobial peptides and proteins (eg, lysozyme, defensins, and protease inhibitors), antioxidants (eg, superoxide dismutase and glutathione), chemokines, and cytokines, in response to environmental stimuli [2,[12][13][14].…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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“…In addition, IL-1α release by BECs was enhanced in COPD-derived cells by exposure to cigarette smoke extract. Although this in vitro model may not completely recapitulate the in vivo situation, it provides important new insights regarding the signals delivered by airway epithelial cells and regulating mesenchymal cells.There is accumulating evidence that BECs are key cells in frontline defence that directly signal to immune cells, in particular antigen-presenting cells [3,4]. Several previous works identified that BECs shape the immune response engaged by pathogens [5].…”

mentioning

confidence: 99%

“…There is accumulating evidence that BECs are key cells in frontline defence that directly signal to immune cells, in particular antigen-presenting cells [3,4]. Several previous works identified that BECs shape the immune response engaged by pathogens [5].…”

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confidence: 99%

Interleukin-1α: a key player for epithelial-to-mesenchymal signalling in COPD?

2016

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@ERSpublicationsInterleukin-1 alpha released by airway epithelial cells may instruct fibroblasts to become proinflammatory in COPD http://ow.ly/CLYK301tyOjThe lungs are continuously exposed to inhaled particles and irritants. Tobacco smoking is the leading cause of several airway diseases, including lung cancer, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In COPD, repeated exposure to cigarette smoke induces chronic inflammation and structural remodelling of the airways, with peribronchial fibrosis and epithelial-to-mesenchymal transition [1], resulting in (mostly irreversible) airway obstruction. Thus, abnormal airway responses to noxious gases probably results from aberrant signalling and crosstalk between epithelial, mesenchymal and immune cells.In this issue of the European Respiratory Journal, OSEI et al.[2] describe how epithelial cells signal to fibroblasts through interleukin (IL)-1α, with relevance to COPD. Using co-cultures of human primary cells (bronchial epithelial cells (BECs) and lung fibroblasts) and human cell lines (MRC5 fetal fibroblasts and 16HBE epithelial cells), the authors show that co-culture of BECs and fibroblasts induced the production of heat shock protein (Hsp)70, IL-8/CXCL8 and IL-1β by lung fibroblasts, while decreasing expression of α-smooth muscle actin, transforming growth factor (TGF)-β1 and extracellular matrix proteins. These effects, which were not different between control-and COPD-derived cells, were recapitulated by using BEC (16HBE)-conditioned medium, suggesting the requirement for soluble factor(s). Using neutralising antibodies, the authors went on to demonstrate that release of CXCL8 and Hsp70 by fibroblasts in the co-culture system was independent of IL-1β and prostaglandin E2 but dependent on IL-1α. In addition, IL-1α release by BECs was enhanced in COPD-derived cells by exposure to cigarette smoke extract. Although this in vitro model may not completely recapitulate the in vivo situation, it provides important new insights regarding the signals delivered by airway epithelial cells and regulating mesenchymal cells.There is accumulating evidence that BECs are key cells in frontline defence that directly signal to immune cells, in particular antigen-presenting cells [3,4]. Several previous works identified that BECs shape the immune response engaged by pathogens [5]. For instance, BECs exposed to Klebsiella pneumoniae regulate local immune responses notably by acting on the myeloid dendritic cell network [6]. Respiratory syncytial virus-infected BECs regulate CD8 + T-cell activation and antiviral activity, according to changes in epithelial expression of the "checkpoint" immune receptor PD-L1 [7]. BECs also regulate dendritic cell differentiation and maturation as well as responsiveness to lipopolysaccharide [8], and inhibit T-cell recall responses towards common aeroallergens in order to ensure mucosal homeostasis and dampen allergic responses [9]. It has also been shown in asthma that BECs may suppress constitutive and IgE-depen...

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Chronic inflammatory airway diseases: the central role of the epithelium revisited

Cited by 72 publications

References 178 publications

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

Interleukin-1α: a key player for epithelial-to-mesenchymal signalling in COPD?

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