Patients with chronic obstructive pulmonary disease(COPD)who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema.This implies the potential involvement of eosinop...Patients with chronic obstructive pulmonary disease(COPD)who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema.This implies the potential involvement of eosinophils in the development of emphysema.However,the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear.In this study,we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema,followed by functional analyses of these subgroups.Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma.Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema.A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix,thereby leading to emphysema in pulmonary tissue Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model.Importantly,eosinophil levels correlated positively with serum cathepsin L levels,which were higher in emphysema patients than those without emphysema.Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients.Collectively,these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling,and its relevance to emphysema in coPD patients.Consequently,targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients.Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.展开更多
基金the National Natural Science Foundation of China(81970036)the Natural Science Foundation of Beijing(7202130)the CAMS Innovation Fund for Medical Sciences(2021-12M-1-049 and 2022-12M-C&T-B-107).
文摘Patients with chronic obstructive pulmonary disease(COPD)who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema.This implies the potential involvement of eosinophils in the development of emphysema.However,the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear.In this study,we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema,followed by functional analyses of these subgroups.Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma.Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema.A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix,thereby leading to emphysema in pulmonary tissue Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model.Importantly,eosinophil levels correlated positively with serum cathepsin L levels,which were higher in emphysema patients than those without emphysema.Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients.Collectively,these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling,and its relevance to emphysema in coPD patients.Consequently,targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients.Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.
