Neutrophils are the first key effector innate immune cells recruited toward inflammatory sites.Through the release of neutrophilic extracellular traps(NETs),the production of reactive oxygen species(ROS),degranulation...Neutrophils are the first key effector innate immune cells recruited toward inflammatory sites.Through the release of neutrophilic extracellular traps(NETs),the production of reactive oxygen species(ROS),degranulation and phagocytosis,neutrophils play a central role in the rapid elimination of invading pathogens.Recently,increasing attention has been given to the role of neutrophils in chronic inflammation,challenging the dichotomy between innate and adaptive immune responses.In chronic inflammatory conditions,neutrophils generally display a hyperinflammatory phenotype via dysregulated pathogen defense mechanisms.Excessive neutrophil activation may result in aberrant cell death,uncontrolled oxidative burst or NET formation and sustained release of inflammatory mediators such as proteases and inflammatory cytokines.Therefore,neutrophils contribute to the development of a sustained inflammatory environment and cause collateral tissue damage.In addition to their direct inflammatory effects,neutrophils further orchestrate inflammation and tissue remodeling by actively engaging in crosstalk with other cells within the immune microenvironment,such as endothelial cells,monocytes,platelets,and T and B cells.This review summarizes the current knowledge of the emerging role of neutrophils in the context of chronic inflammation.The key characteristics of neutrophils and their interactions with distinct cell types are discussed within the initial part of the review,whereas the second part focuses on their contributions to the pathophysiology of immune-driven diseases,including rheumatoid arthritis,atherosclerosis,inflammatory bowel disease,systemic lupus erythematosus,chronic obstructive pulmonary disease,and fibrotic disorders.Increasing knowledge on neutrophil behavior in the context of chronic inflammation may offer novel insights into disease pathology and,potentially,the identification of novel therapeutic targets.展开更多
基金supported by grants from KU Leuven(C1 grant C14/23/143)received funding under the Horizon Europe programme within the MSCA-DN project B-ACTIVE(grant 101120187)+1 种基金Kaat Torfs and Gaël Vermeersch hold a personal PhD fellowship for Fundamental Research from FWO Vlaanderen(1139025N and 1144825N)MG is financially supported by the Rega Foundation.
文摘Neutrophils are the first key effector innate immune cells recruited toward inflammatory sites.Through the release of neutrophilic extracellular traps(NETs),the production of reactive oxygen species(ROS),degranulation and phagocytosis,neutrophils play a central role in the rapid elimination of invading pathogens.Recently,increasing attention has been given to the role of neutrophils in chronic inflammation,challenging the dichotomy between innate and adaptive immune responses.In chronic inflammatory conditions,neutrophils generally display a hyperinflammatory phenotype via dysregulated pathogen defense mechanisms.Excessive neutrophil activation may result in aberrant cell death,uncontrolled oxidative burst or NET formation and sustained release of inflammatory mediators such as proteases and inflammatory cytokines.Therefore,neutrophils contribute to the development of a sustained inflammatory environment and cause collateral tissue damage.In addition to their direct inflammatory effects,neutrophils further orchestrate inflammation and tissue remodeling by actively engaging in crosstalk with other cells within the immune microenvironment,such as endothelial cells,monocytes,platelets,and T and B cells.This review summarizes the current knowledge of the emerging role of neutrophils in the context of chronic inflammation.The key characteristics of neutrophils and their interactions with distinct cell types are discussed within the initial part of the review,whereas the second part focuses on their contributions to the pathophysiology of immune-driven diseases,including rheumatoid arthritis,atherosclerosis,inflammatory bowel disease,systemic lupus erythematosus,chronic obstructive pulmonary disease,and fibrotic disorders.Increasing knowledge on neutrophil behavior in the context of chronic inflammation may offer novel insights into disease pathology and,potentially,the identification of novel therapeutic targets.
