期刊
CELL REPORTS
卷 41, 期 11, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.111797
关键词
-
类别
资金
- Cystic Fibrosis Foundation [OZ18F0, BRUSCI20G0, EGAN16G0, ESQUIB19H0]
- National Institutes of Health (NIH) [R01HL157776, R01AI153422]
- NIH/NIDDK [U54DK106857, R01DK124788]
- NIH/NIDDK Cooperative Centers of Excellence in Hematology (CCEH) [U24DK126127]
- AIRC [24883]
This study identifies CCR2+ monocytes as a previously neglected contributor to lung damage in CF, driving pathogenic TGF-β signaling and sustaining inflammation by facilitating neutrophil recruitment. Targeting CCR2 to reduce monocyte numbers in CF lungs can ameliorate neutrophil inflammation and prevent tissue damage.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据