CORAUX Christelle
@univ-reims.fr
Scopus Publications
- Electrolyte-rich saline solutions significantly improve nasal epithelial repair, ciliary beating and epithelial inflammation vs. normal saline
Ludovic de Gabory, Christelle Coraux, Anne Beaulieu, Mélodie Kerimian
European Archives of Oto Rhino Laryngology, 2026 - Peptide CIGB-552 has a synergistic effect on CFTR-F508del when combined with elexacaftor/tezacaftor/ivacaftor triple therapy for cystic fibrosis
Benjamin Simonneau, Stéphanie Simon, Bénédicte Duriez, Aurélie Guguin, Frédéric Becq, et al.
British Journal of Pharmacology, 2025
Background and PurposeCystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene, leading to progressive respiratory decline and reduced life expectancy. The most common mutation, CFTR‐F508del, results in mislocalised and non‐functional protein. Although triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) is prescribed for patients carrying this mutation, some biological defects remain unresolved. We previously identified COMMD1 as a potential therapeutic target, as its overexpression enhances CFTR‐WT plasma membrane localisation. CIGB‐552, a cell‐penetrating peptide discovered in 2013, stabilises COMMD1. This study evaluates its therapeutic potential in cystic fibrosis.Experimental ApproachCIGB‐552 was tested, with and without ETI, in CFBE and HEK cells stably expressing CFTR‐WT or CFTR‐F508del, and in primary human bronchial cells. CFTR function was assessed using YFP quenching and short‐circuit current assays. Peptide uptake was evaluated using FITC‐labelled CIGB‐552 in submerged and air–liquid interface models. Plasma membrane density of CFTR was measured in CFBE CFTR‐HA cells, and western blotting assessed CFTR maturation and COMMD1 expression.Key resultsCIGB‐552 was non‐toxic and preferentially entered CFBE CFTR‐F508del cells rather than CFBE CFTR‐WT cells, without altering COMMD1 expression or localisation. Although not a corrector or potentiator alone, CIGB‐552 synergised with ETI, enhancing CFTR‐F508del‐mediated chloride efflux, confirmed in primary cells. CIGB‐552 also increased YFP quenching of CFTR‐WT and CFTR‐G551D, in combination with ivacaftor. This effect required COMMD1.Conclusions and ImplicationsCOMMD1 expression was necessary for CIGB‐552 to affect CFTR function positively. Its synergy with the triple therapy offers a promising strategy for improving CF treatment. - Low-molecular-weight hyaluronic acid improves regeneration of cystic fibrosis airway epithelium
Damien Adam, Emilie Luczka-Majérus, Julie Cellier, Charline Dos Santos-Dietz, Claire Kileztky, et al.
Erj Open Research, 2025
Background Cystic fibrosis is characterised by defective mucociliary clearance, chronic lung infection and exaggerated neutrophilic inflammation. Airway epithelium damage and remodelling affect lung defence functions and are therefore important components of lung pathology progression in cystic fibrosis. Identifying compounds that favour mucociliary clearance by improving airway epithelial structure and regeneration is therefore crucial for patients with cystic fibrosis. Materials and methods Using air–liquid interface culture of human airway epithelial cells obtained from patients with cystic fibrosis, we examined the influence of low-molecular-weight hyaluronic acid (LMW-HA) (∼40 kDa) on the regeneration and remodelling of cystic fibrosis human airway epithelial cells. Results Our results show that LMW-HA normalises cystic fibrosis epithelial regeneration, even in an inflamed environment, by preventing remodelling in terms of epithelial height and basal cell hyperplasia, by avoiding inflammation-related goblet cell hyperplasia and by stimulating multiciliated cell differentiation. Because remodelling is mainly due to either intrinsic inflammation of cystic fibrosis human airway epithelial cells or an extrinsic inflammatory environment, we examined the impact of LMW‑HA on epithelial interleukin 8 pro-inflammatory chemokine and found that it exerts an anti-inflammatory effect, evidenced by reduced epithelial interleukin 8 expression and secretion. Conclusion We report here that LMW-HA prevents cystic fibrosis human airway epithelial cell remodelling and normalises its cell structure, probably through the epithelial cell inflammatory phenotype modulation, and improves multiciliated cell differentiation by a mechanism that is independent of its anti-inflammatory effect. These results demonstrate that LMW-HA should be considered as a therapeutic candidate for the treatment of cystic fibrosis lung disease. - Roscovitine enhances the bactericidal activity of the airway surface liquid of the cystic fibrosis bronchial epithelium but does not protect against Pseudomonas aeruginosa infection
Adrien Maupas, Anaëlle Muggeo, Pierre Vermeulen, Sophie Moussalih, Edouard Sage, et al.
Plos One, 2025
Cystic fibrosis (CF) is the most common genetic diseases in the Caucasian population. CFTR defects, the most common being F508del, lead to abnormal mucus accumulation. Respiratory failure caused by the resulting chronic infections is the leading cause of death in people with cystic fibrosis (pwCF). Pseudomonas aeruginosa is a major pathogen in CF and is responsible for a deterioration of respiratory function in pwCF. The increase of antibiotic-resistant P. aeruginosa strains encourages the search for alternative therapeutics for treating P. aeruginosa infection. In vitro studies have shown an interest in (R)-roscovitine (roscovitine) in the fight against bacterial infection in pwCF. Here we show a nuanced effect of roscovitine on ASL bactericidal activity and CF bronchial epithelium protection against P. aeruginosa. Using a 3D model of fully differentiated and functional F508del-CFTR human bronchial epithelium, we evidenced (i) an enhancement of the bactericidal activity of the airway surface liquid for 25 μM roscovitine but (ii) no limitation of the dynamic of the epithelium destruction upon roscovitine treatment whatever the concentrations. Our findings shed light on reasons for the lack of beneficial effects to prevent P. aeruginosa infection in pwCF treated with roscovitine in the ROSCO-CF clinical trial. We anticipate that our findings would have significant therapeutic implications in seeking to optimize roscovitine analogs. - The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca2+-mobilizing agonists normalizing abnormal Ca2+ levels in human airway epithelial cells
Manuella Lévêque, Sandra Mirval, Christine Barrault, Isabelle Fixe, Christelle Coraux, et al.
Respiratory Research, 2024 - The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells
Raphaël Santinelli, Nathalie Benz, Julie Guellec, Fabien Quinquis, Ervin Kocas, et al.
Cells, 2024
Cystic Fibrosis (CF) is present due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, the most frequent variant being p.phe508del. The CFTR protein is a chloride (Cl-) channel which is defective and almost absent of cell membranes when the p.Phe508del mutation is present. The p.Phe508del-CFTR protein is retained in the endoplasmic reticulum (ER) and together with inflammation and infection triggers the Unfolded Protein Response (UPR). During the UPR, the Activating Transcription Factor 6 (ATF6) is activated with cleavage and then decreases the expression of p.Phe508del-CFTR. We have previously shown that the inhibition of the activation of ATF6 alleviates the p.Phe508del-CFTR defects in cells overexpressing the mutated protein. In the present paper, our aim was to inhibit the cleavage of ATF6, and thus its activation in a human bronchial cell line with endogenous p.Phe508del-CFTR expression and in bronchial cells from patients, to be more relevant to CF. This was achieved by inhibiting the protease MBTP1 which is responsible for the cleavage of ATF6. We show here that this inhibition leads to increased mRNA and p.Phe508del-CFTR expression and, consequently, to increased Cl-efflux. We also explain the mechanisms linked to these increases with the modulation of genes when MBTP1 is inhibited. Indeed, RT-qPCR assays show that genes such as HSPA1B, CEBPB, VIMP, PFND2, MAPK8, XBP1, INSIG1, and CALR are modulated. In conclusion, we show that the inhibition of MBTP1 has a beneficial effect in relevant models to CF and that this is due to the modulation of genes involved in the disease. - IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology
Olivia Barada, Sophie Salomé-Desnoulez, Fahima Madouri, Gaëtan Deslée, Christelle Coraux, et al.
Cells, 2023
Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. Methods: The expression of IL-20 cytokines and their receptors was investigated in lung-derived samples collected from non-COPD and COPD patients, from mice chronically exposed to cigarette smoke and from airway epithelial cells from humans and mice exposed in vitro to cigarette smoke. To investigate the role of IL-20 cytokines in wound healing, experiments were performed using a blocking anti-IL-20Rb antibody. Results: Of interest, IL-20 cytokines and their receptors were expressed in bronchial mucosa, especially on airway epithelial cells. Their expression correlated with the disease severity. Blocking these cytokines in a COPD context improved the repair processes after a lesion induced by scratching the epithelial layer. Conclusions: Collectively, this study highlights the implication of IL-20 cytokines in the repair of the airway epithelium and in the pathology of COPD. IL-20 subfamily cytokines might provide therapeutic benefit for patients with COPD to improve epithelial healing. - Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium
Anaëlle Muggeo, Christelle Coraux, Thomas Guillard
Plos Pathogens, 2023
Pseudomonas aeruginosa is a major, but opportunistic, respiratory pathogen, which rarely infects healthy individuals, mainly due to the barrier effect of the human airway epithelium (HAE). This review explores the interaction of P. aeruginosa with HAE and the progression of the infection. The basolateral part of the epithelium, which includes the basolateral membrane of the epithelial cells and the basement membrane, is inaccessible in normal tight epithelia with intact junctions. We highlight how P. aeruginosa exploits weaknesses in the HAE barrier to gain access to the basolateral part of the epithelium. This access is crucial to initiate respiratory infection and is mainly observed in the injured epithelium, in repairing or chronically remodeled epithelium, and during extrusion of senescent cells or cell multiplication during normal epithelium renewal. The subsequent adhesion of the bacteria and cytotoxic action of virulence factors, including the toxins delivered by the type 3 secretion system (T3SS), lead to retractions and cell death. Eventually, P. aeruginosa progressively reaches the basement membrane and propagates radially through the basal part of the epithelium to disseminate using twitching and flagellar motility. - Involvement of inorganic phosphate starvation in Pseudomonas aeruginosa bacterial virulence
L. Jahdauti, A. Muggeo, V. Paturel, S. Jaisson, E. Luczka, et al.
Revue Des Maladies Respiratoires, 2023 - Ciliogenesis is intrinsically altered in COPD small airways
Emilie Luczka-Majérus, Arnaud Bonnomet, Adeline Germain, Nathalie Lalun, Claire Kileztky, et al.
European Respiratory Journal, 2022
COPD is characterised by a progressive and irreversible airflow limitation due to airway obstruction and emphysema [1]. We and others showed that bronchial epithelial remodelling in COPD is characterised by alteration of ciliogenesis and cilia function [2, 3], as well as a dysregulation of non-motile primary cilia (PC) [4]. In COPD, the main site of obstruction is in the small airways [5]. Considering that COPD is foremost a small airway disease (SAD) [6–8], we investigated the differentiation of bronchiolar epithelium in COPD, focusing on motile and primary ciliogenesis. An alteration of primary and motile ciliogenesis is detected in mild/moderate COPD small airways and could be at the origin of the initiation of epithelial remodelling http://bit.ly/3Tz3JDj - Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity
Antony Hoarau, Myriam Polette, Christelle Coraux
Biomolecules, 2022 - The rescue of F508del-CFTR by elexacaftor/tezacaftor/ivacaftor (Trikafta) in human airway epithelial cells is underestimated due to the presence of ivacaftor
Frédéric Becq, Sandra Mirval, Thomas Carrez, Manuella Lévêque, Arnaud Billet, et al.
European Respiratory Journal, 2022 - Short-term consequences of F508del-CFTR thermal instability on CFTR-dependent transepithelial currents in human airway epithelial cells
Lionel Froux, Christelle Coraux, Edouard Sage, Frédéric Becq
Scientific Reports, 2019 - Involvement of the Prion Protein in the Protection of the Human Bronchial Epithelial Barrier Against Oxidative Stress
Amal Kouadri, Mariam El Khatib, Johanna Cormenier, Sylvain Chauvet, Wael Zeinyeh, et al.
Antioxidants and Redox Signaling, 2019 - Inactivation of the interleukin-22 pathway in the airways of cystic fibrosis patients
Antoine Guillon, Deborah Brea, Emilie Luczka, Virginie Hervé, Soujoud Hasanat, et al.
Cytokine, 2019 - Alteration of primary cilia in COPD
Jeanne-Marie Perotin, Christelle Coraux, Eymeric Lagonotte, Philippe Birembaut, Gonzague Delepine, et al.
European Respiratory Journal, 2018 - MicroRNA-9 downregulates the ANO1 chloride channel and contributes to cystic fibrosis lung pathology
Florence Sonneville, Manon Ruffin, Christelle Coraux, Nathalie Rousselet, Philippe Le Rouzic, et al.
Nature Communications, 2017 - Buserelin alleviates chloride transport defect in human cystic fibrosis nasal epithelial cells
Marie-Laure Calvez, Nathalie Benz, Florentin Huguet, Aude Saint-Pierre, Elise Rouillé, et al.
Plos One, 2017 - Non-diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline
Arnaud Bonnomet, Emilie Luczka, Christelle Coraux, Ludovic de Gabory
International Forum of Allergy and Rhinology, 2016 - In vitro and in vivo evidence for an inflammatory role of the calcium channel TRPV4 in lung epithelium: Potential involvement in cystic fibrosis
Clémence O. Henry, Emilie Dalloneau, Maria-Teresa Pérez-Berezo, Cristina Plata, Yongzheng Wu, et al.
American Journal of Physiology Lung Cellular and Molecular Physiology, 2016 - Cystic fibrosis airway epithelium remodelling: Involvement of inflammation
Damien Adam, Jacqueline Roux-Delrieu, Emilie Luczka, Arnaud Bonnomet, Julien Lesage, et al.
Journal of Pathology, 2015 - Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity
Jeanne-Marie Perotin, Damien Adam, Juliette Vella-Boucaud, Gonzague Delepine, Sebastian Sandu, et al.
Respiratory Research, 2014 - Regeneration of airway epithelium
D. Adam, J.-M. Perotin, F. Lebargy, P. Birembaut, G. Deslée, et al.
Revue Des Maladies Respiratoires, 2014 - Contribution of α7 nicotinic receptor to airway epithelium dysfunction under nicotine exposure
Kamel Maouche, Kahina Medjber, Jean-Marie Zahm, Franck Delavoie, Christine Terryn, et al.
Proceedings of the National Academy of Sciences of the United States of America, 2013 - Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue
Nguyen Thu Ngan Trinh, Olivier Bardou, Anik Privé, Emilie Maillé, Damien Adam, et al.
European Respiratory Journal, 2012
