Interdisciplinary approaches for COPD understanding
Group leader: Isabelle Dupin
Group members: Léo Grassion, Pauline Henrot, Eloïse Latouille, Amélie Legrix, Elise Maurat, Renaud Prevel, Katharina Raasch, Maeva Zysman
Lung exposure to various types of particles, such as those present in cigarette smoke, can lead to chronic obstructive pulmonary disease (COPD). COPD is a common and devastating respiratory disease, characterized by a progressive airflow obstruction. The chronic course of COPD is frequently worsened by acute exacerbations, which contribute considerably to the worldwide increased mortality, morbidity, and health-care costs. In addition, around 1/3 of individuals with COPD present skeletal muscle damage, also known as sarcopenia (Henrot et al., 2023a; b), which is itself responsible for increased morality among patients with COPD.
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We hypothesize that alterations in cell-cell and cell-matrix interactions are a major cause of chronic inflammation, fibrotic manifestations and destructive lesions (emphysema) in the lungs and skeletal muscles of patients with COPD. Our group aims at combining basic and translational approaches together with a combination of advanced imaging, innovative cellular and animal models to investigate the interaction between cells and their microenvironment, in the context of COPD and air pollution. Thanks to the close relationship with the University hospital of Bordeaux and physicians from the research group, we have a privileged access to human lung and muscle samples.
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Recent achievements
Recently, we have demonstrated the key role of fibrocytes, circulating cells of monocytic origin and with fibroblast properties, in perpetuating chronic inflammation, through interaction with and activation of CD8+ T cells (Dupin et al., 2019; Eyraud et al., 2023; Henrot et al., 2021). We have also shown that the CXCL12/CXCR4 axis plays a key role in the pathogenesis of early COPD, supporting further investigation into the use of CXCR4 inhibitors to slow down the progression of COPD (Dupin et al., 2023; Henrot et al., 2019). We have recently oriented our interest towards more physiological tridimensional culture models to investigate mechanisms leading to respiratory disease development (Maurat et al., 2024) and to test innovative treatments, with the ambition of moving towards personalized medicine for individuals with COPD.
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Current projects
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To investigate the response to particulate pollution and mechanisms of lung resilience using novel organoid model of distal airways and mathematical models
PI: Isabelle Dupin
Main fundings: ERC CoG KINTSUGI, ANR JCJC BRONCHIOLE
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To develop a standardized alveolosphere model to better understand emphysema pathophysiology
PI: Maeva Zysman
Main fundings: ANR PRCE LUMEN, Fondation du Souffle, Chiesi
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To study the role of satellite cells and CXCL12/CXCR4 axis in the development of COPD-associated sarcopenia using animal models and innovative skeletal muscle organoid
PI: Pauline Henrot
Main fundings: ANR PRC SCOOP, RIE Univ Bordeaux
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To evaluate the efficacy of innovative curative RNA drugs, that could counteract bronchial remodeling and chronic inflammation in COPD
PI: Isabelle Dupin
Main fundings: ANR PRC LUNATA, AstraZeneca
Main references
A novel in vitro tubular model to recapitulate features of distal airways: The bronchioid.
Maurat, E, K. Raasch, A. Leipold, P. Henrot, M. Zysman, R. Prevel, T. Trian, T. Krammer, V. Bergeron, M. Thumerel, P. Nassoy, P. Berger, A-E. Saliba, L. Andrique, G. Recher, I. Dupin.
Eur Respir J. 2024. DOI:10.1183/13993003.00562-2024.
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CXCR4 blockade alleviates pulmonary and cardiac outcomes in young COPD.
Dupin, I., P. Henrot, E. Maurat, R. Abohalaka, S. Chaigne, D.E. Hamrani, E. Eyraud, R. Prevel, P. Esteves, M. Campagnac, M. Dubreuil, G. Cardouat, C. Bouchet, O. Ousova, J.-W. Dupuy, T. Trian, M. Thumerel, H. Begueret, P.-O. Girodet, R. Martan, M. Zysman, V. Michel, and P. Berger.
BioRXiv. 2023 DOI:10.1101/2023.03.10.529743.
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Nizamoglu M, Joglekar MM, Almeida CR, Larsson Callerfelt AK, Dupin I, Guenat OT, Henrot P, van Os L, Otero J, Elowsson L, Farre R, Burgess JK.
Eur Respir Rev. 2023. DOI: 10.1183/16000617.0042-2023.
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Eyraud, E., E. Maurat, J-M. Sac-Epée, P. Henrot, M. Zysman, P. Esteves, T. Trian, J-W. Dupuy, A. Leopold, A-E. Saliba, H. Bégueret, P-O. Girodet, M. Thumerel, R. Hustache-Castaing, R. Marthan, F. Levet, P. Vallois, C. Contin-Bordes, P. Berger, I. Dupin.
eLife. 2023 DOI: 10.7554/eLife.85875.
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Dupin, I., E. Eyraud, E. Maurat, J.-M. Sac-Épée, and P. Vallois.
Journal of Theoretical Biology. 2023. 564:111448. DOI:10.1016/j.jtbi.2023.111448.
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Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models.
Henrot P, Blervaque L, Dupin I, Zysman M, Esteves P, Gouzi F, Hayot M, Pomiès P, Berger P.
J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):745-757. DOI: 10.1002/jcsm.13103.
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Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting.
Henrot P, Dupin I, Schilfarth P, Esteves P, Blervaque L, Zysman M, Gouzi F, Hayot M, Pomiès P, Berger P.
Int J Mol Sci. 2023 Mar 29;24(7):6454. DOI: 10.3390/ijms24076454.
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Muscarinic receptor M3 activation promotes fibrocytes contraction.
Henrot, P., E. Eyraud, E. Maurat, S. Point, G. Cardouat, J-F. Quignard, P. Esteves, T. Trian, P-O Girodet, R. Marthan, M. C. Zysman, P. Berger, I. Dupin.
Frontiers in Pharmacology. 2022 DOI.org/10.3389/fphar.2022.939780.
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Circulating fibrocytes as a new tool to predict lung cancer progression after surgery?
Henrot P, Beaufils F, Thumerel M, Eyraud E, Boudoussier A, Begueret H, Maurat E, Girodet PO, Marthan R, Berger P, Dupin I, Zysman M.
Eur Respir J. 2021 Sep 24:2101221. DOI: 10.1183/13993003.01221-2021.
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Determination of reliable lung function parameters in intubated mice.
Bonnardel E, Prevel R, Campagnac M, Dubreuil M, Marthan R, Berger P, Dupin I.
Respir Res 2019, 20:211. DOI: 10.1186/s12931-019-1177-9.
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Fibrocyte accumulation in the airway walls of COPD patients.
Dupin I, Thumerel M, Maurat E, Coste F, Eyraud E, Begueret H, Trian T, Montaudon M, Marthan R, Girodet PO, Berger P.
Eur Respir J 2019, 54. DOI:10.1183/13993003.02173-2018
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Chemokines in COPD: From Implication to Therapeutic Use.
Henrot P, Prevel R, Berger P, Dupin I.
Int J Mol Sci 2019, 20. DOI: 10.3390/ijms20112785