Alteration of primary cilia in COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a major economic and social concern worldwide because of its impact on mortality and morbidity [1]. COPD is characterised by airway epithelium remodelling, a hallmark of dysregulated airway epithelium plasticity [2]. There are currently no available therapeutics to restore the integrity and functionality of the epithelium. Therefore, novel sources of investigation are becoming crucial to understand the alterations at the root of COPD initiation. Non-motile primary cilia are solitary sensor organelles playing a critical role in cell cycle control, proliferation, polarity and differentiation, particularly of ciliated cells possessing motile cilia [3, 4]. Primary cilia are assembled on different types of human cells depending on their state and activities in response to cellular quiescence where they relay extracellular signals and retract upon cell cycle re-entry [5]. Alterations of primary cilium structure and function are responsible for ciliopathies [6, 7]. Primary cilia may be crucial in determining outcomes during airway epithelial cell differentiation thus we hypothesised that primary cilia are present in adult epithelial cells and may play a key role in airway plasticity. First, we investigated the presence and localisation of primary cilia in the bronchial epithelium. Secondly, we analysed the relationships between primary cilia and clinical, functional and histological characteristics of non-COPD and COPD patients.

Airway epithelial cell differentiation relies on deficient Hedgehog signalling in COPD

“…Alterations of the presence, structure and function of cilia on differentiated AEC were not completely elucidated while the mucociliary clearance was often seen as a readout of normal lung function [70,71]. Mucins secretion was not significantly impacted although there was a trend favouring Muc5b producing cells despite the reduction of MUC5AC and MUC5B transcripts at the beginning of differentiation, therefore it will be interesting to fully characterize cilia and goblet cells alterations upon HH inhibition to understand the molecular events leading to epithelial remodelling particularly since we also observed primary cilia defects in COPD patients [50].…”

“…Immunohistochemistry was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues distant from the tumour as previously described [50] and frozen tissues. Five 5 μm sections were processed for H&E staining and observed on microscope (x20) to confirm the presence of bronchi.…”

In Vitro Models for Studying Respiratory Host–Pathogen Interactions

“…[ 79,80,119 ] These are used to study levels of inflammatory markers and immune cell activity, which may also form the basis for patient stratification and treatment. It is also possible to study markers of mucociliary clearance, such as levels of ciliary metaplasia [ 80,120 ] and ciliary beat frequency, [ 79 ] the reduction of which may increase patient vulnerability to infection and sputum production. An altered respiratory microbiota is also implicated in COPD pathophysiology, [ 121 ] with acute exacerbations linked to microbial–pathogen interactions and infection.…”

Altered generation of ciliated cells in chronic obstructive pulmonary disease

“…Recently, Perotin et al . showed that primary cilia (non-motile) are dysregulated in COPD patients both in remodelled and non-remodelled epithelium 9 . More broadly, ciliopathies are particularly prone to induce cystic diseases at various sites, notably the lung in primary ciliary dyskinesia (bronchiectasis) or the kidneys (in polycystic kidney disease) 10,11 .…”