Persistent neutrophil-dominated lung inflammation contributes to lung damage in cystic fibrosis (CF). How-ever, the mechanisms that drive persistent lung neutrophilia and tissue deterioration in CF are not well characterized. Starting from the observation that, in patients with CF, c-c motif chemokine receptor 2 (CCR2)+ monocytes/macrophages are abundant in the lungs, we investigate the interplay between mono-cytes/macrophages and neutrophils in perpetuating lung tissue damage in CF. Here we show that CCR2+ monocytes in murine CF lungs drive pathogenic transforming growth factor (3 (TGF-(3) signaling and sustain a pro-inflammatory environment by facilitating neutrophil recruitment. Targeting CCR2 to lower the numbers of monocytes in CF lungs ameliorates neutrophil inflammation and pathogenic TGF-(3 signaling and prevents lung tissue damage. This study identifies CCR2+ monocytes as a neglected contributor to the pathogenesis of CF lung disease and as a therapeutic target for patients with CF, for whom lung hyperinflammation and tissue damage remain an issue despite recent advances in CF transmembrane conductance regulator (CFTR)-specific therapeutic agents.

Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis / Öz, Hasan H; Cheng, Ee-Chun; Di Pietro, Caterina; Tebaldi, Toma; Biancon, Giulia; Zeiss, Caroline; Zhang, Ping-Xia; Huang, Pamela H; Esquibies, Sofia S; Britto, Clemente J; Schupp, Jonas C; Murray, Thomas S; Halene, Stephanie; Krause, Diane S; Egan, Marie E; Bruscia, Emanuela M. - In: CELL REPORTS. - ISSN 2211-1247. - 41:11(2022), pp. 11179701-111797e6. [10.1016/j.celrep.2022.111797]

Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis

Tebaldi, Toma;
2022-01-01

Abstract

Persistent neutrophil-dominated lung inflammation contributes to lung damage in cystic fibrosis (CF). How-ever, the mechanisms that drive persistent lung neutrophilia and tissue deterioration in CF are not well characterized. Starting from the observation that, in patients with CF, c-c motif chemokine receptor 2 (CCR2)+ monocytes/macrophages are abundant in the lungs, we investigate the interplay between mono-cytes/macrophages and neutrophils in perpetuating lung tissue damage in CF. Here we show that CCR2+ monocytes in murine CF lungs drive pathogenic transforming growth factor (3 (TGF-(3) signaling and sustain a pro-inflammatory environment by facilitating neutrophil recruitment. Targeting CCR2 to lower the numbers of monocytes in CF lungs ameliorates neutrophil inflammation and pathogenic TGF-(3 signaling and prevents lung tissue damage. This study identifies CCR2+ monocytes as a neglected contributor to the pathogenesis of CF lung disease and as a therapeutic target for patients with CF, for whom lung hyperinflammation and tissue damage remain an issue despite recent advances in CF transmembrane conductance regulator (CFTR)-specific therapeutic agents.
2022
11
Öz, Hasan H; Cheng, Ee-Chun; Di Pietro, Caterina; Tebaldi, Toma; Biancon, Giulia; Zeiss, Caroline; Zhang, Ping-Xia; Huang, Pamela H; Esquibies, Sofia S; Britto, Clemente J; Schupp, Jonas C; Murray, Thomas S; Halene, Stephanie; Krause, Diane S; Egan, Marie E; Bruscia, Emanuela M
Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis / Öz, Hasan H; Cheng, Ee-Chun; Di Pietro, Caterina; Tebaldi, Toma; Biancon, Giulia; Zeiss, Caroline; Zhang, Ping-Xia; Huang, Pamela H; Esquibies, Sofia S; Britto, Clemente J; Schupp, Jonas C; Murray, Thomas S; Halene, Stephanie; Krause, Diane S; Egan, Marie E; Bruscia, Emanuela M. - In: CELL REPORTS. - ISSN 2211-1247. - 41:11(2022), pp. 11179701-111797e6. [10.1016/j.celrep.2022.111797]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/369967
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