Bronchial remodeling in COPD
Group leader Isabelle Dupin
Lung exposure to various types of particules, such as those present in cigarette smoke, can lead to chronic obstructive pulmonary disease (COPD). COPD is a common and devastating respiratory disease, characterized to a progressive airflow obstruction. The disease is characterized by chronic inflammation and bronchial remodeling, in particular peribronchial fibrosis. The chronic course of COPD is frequently worsened by acute exacerbations, which contribute considerably to the worldwide increased mortality, morbidity, and health-care costs associated with the disease. None of the drugs labeled on the COPD market have a significant effect on mortality of COPD patients. Our group is interested in the role of fibrocytes, fibroblast-like cells produced by of the bone marrow, in COPD. These cells can circulate can circulate in the blood and can be recruited into injured tissues (Dupin et al., 2018). We have shown that the level of circulating fibrocytes in peripheral blood is increased during acute exacerbations of COPD patients and that the CXCR4-CXCL12 axis is important for COPD fibrocyte migration (Dupin et al., 2016).
We have recently demonstrated an increase of tissue fibrocytes in COPD lungs, which is associated with a degraded lung function and anatomical modifications (Dupin et al., 2019). The function of these fibrocytes in COPD lungs is not yet understood.
Fibrocytes may participate to lung inflammation in virtue of their immune properties. As myofibroblast-like cells precursors, fibrocytes could also play a role in peribronchial fibrosis, either directly or indirectly. We will combine basic and translational approaches together with a combination of advanced imaging, innovative cellular and animal models to understand in vivo the recruitment and function(s) of fibrocytes, thereby opening new perspectives for COPD treatment.
The current objectives of the group are the following:
1) To assess the mechanisms of fibrocyte chemotaxis during exacerbation
2) To understand the determinants of the fibrocyte differentiation in the lung
3) To investigate the role of fibrocytes in chronic inflammation
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.
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
Henrot P, Prevel R, Berger P, Dupin I.
Int J Mol Sci 2019, 20. DOI: 10.3390/ijms20112785
Dupin I, Contin-Bordes C, Berger P.
Am J Respir Cell Mol Biol 2018 58:288-298. DOI:10.1165/rcmb.2017-0301PS
Dupin I, Allard B, Ozier A, Maurat E, Ousova O, Delbrel E, Trian T, Bui HN, Dromer C, Guisset O, Blanchard E, Hilbert G, Vargas F, Thumerel M, Marthan R, Girodet PO, Berger P.
J Allergy Clin Immunol 2016; 137: 1036-1042 e1037. DOI:10.1016/j.jaci.2015.08.043