Loss of ciliated cells and altered airway epithelial integrity in cystic fibrosis

Collin, Amandine; Lecocq, Marylène; Detry, Bruno; Carlier, François; Bouzin, Caroline; Sany, Philippe de; Hoton, Delphine; Verleden, Stijn E.; Froidure, Antoine; Pilette, Charles; Gohy, Sophie

doi:10.1016/j.jcf.2021.09.019

Cited by 15 publications

(16 citation statements)

References 37 publications

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“…In addition, TGF-β expression is increased in CF and associated with a thickening of the reticular basement membrane. The presence of EMT and altered differentiation of epithelial cells were confirmed by more recent data that aimed to characterize the abnormal phenotype in CF bronchial epithelium, showing decreased ciliated cells number, increased goblet cells number, and increased mesenchymal markers expression [ 68 ] ( Figure 1 , unpublished data). Interestingly, the EMT sensitivity of CFTR-expressing epithelial cells was reversed by CFTR modulators [ 69 ] while in end-stage CF patients, single-cell transcriptome confirmed altered epithelial differentiation showing fewer basal cells and more cells transitioning to ciliated and secretory cells than in non-CF controls [ 55 ].…”

Section: Alterations Of the Cf Respiratory Epitheliumsupporting

confidence: 53%

Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Gohy

Moeremans

Pilette

et al. 2021

Cells

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The respiratory epithelium represents the first chemical, immune, and physical barrier against inhaled noxious materials, particularly pathogens in cystic fibrosis. Local mucus thickening, altered mucociliary clearance, and reduced pH due to CFTR protein dysfunction favor bacterial overgrowth and excessive inflammation. We aimed in this review to summarize respiratory mucosal alterations within the epithelium and current knowledge on local immunity linked to immunoglobulin A in patients with cystic fibrosis.

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Section: Alterations Of the Cf Respiratory Epitheliumsupporting

confidence: 53%

Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Gohy

Moeremans

Pilette

et al. 2021

Cells

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“…In support of a deranged cilia phenotype, transmission electron microscopy demonstrates that the UIP/IPF distal airways display defects in microtubule organization [ 70 ]. In the context in cystic fibrosis, it is reported that airway epithelial also have decreased ciliated cells with enhanced mucin expression [ 71 ]. Thus, future studies determining the mechanism of deranged ciliogenesis is warranted.…”

Section: Discussionmentioning

confidence: 99%

Morphologically intact airways in lung fibrosis have an abnormal proteome

et al. 2023

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Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression.

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“…Structurally, transmission electron microscopy demonstrates that the UIP/IPF distal airways display defects in microtubule organization, which will have detrimental effect on cilia function [39]. In the context in cystic fibrosis, it is reported that airway epithelial also have decreased ciliated cells with enhanced mucin expression [63]. Thus, future studies determining the mechanism of deranged ciliogenesis is warranted.…”

Section: Discussionmentioning

confidence: 99%

The UIP honeycomb airway cells are the site of mucin biogenesis with deranged cilia

Herrera

Dingle

Montero

et al. 2022

Preprint

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Honeycombing (HC) is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). HC refers to cystic airways (HC airways) located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic HC airway cells and fibrotic uninvolved airway cells (distant from sites of UIP and morphologically intact) in 10 UIP specimens; 6 non-fibrotic airway cell specimens served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 UIP and 6 mucinous adenocarcinoma (MA) specimens. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to HC airway cells, showing deregulation of SLITs and ROBO pathway as the strongest category. We find that BPIFB1 is the most significantly increased secretome-associated protein in UIP, whereas MUC5AC is the most significantly increased in MA. We conclude that spatial proteomics demonstrates that the fibrotic uninvolved airway cells are abnormal. In addition, fibrotic HC airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach will generate novel and testable hypotheses to decipher fibrosis progression.

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Loss of ciliated cells and altered airway epithelial integrity in cystic fibrosis

Cited by 15 publications

References 37 publications

Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Morphologically intact airways in lung fibrosis have an abnormal proteome

The UIP honeycomb airway cells are the site of mucin biogenesis with deranged cilia

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