Nature子刊：CAR-巨噬细胞疗法，治疗炎症性疾病

Core Viewpoint - The article discusses the development of CAR-M (Chimeric Antigen Receptor Macrophages) therapy targeting inflammation, highlighting its potential in treating various inflammatory diseases by converting immune responses into anti-inflammatory effects [7][10]. Group 1: Inflammation and Macrophages - Inflammation plays a critical role in many diseases, and unresolved inflammation can lead to severe outcomes such as organ failure [2]. - Macrophages are strategically located throughout the body and are essential for maintaining homeostasis by clearing pathogens and harmful substances [2]. - M2 macrophages have shown promise in reducing damage in various disease models, but their effectiveness is limited by their phenotypic plasticity, which can lead to pathogenic transformation in inflammatory environments [2][8]. Group 2: CAR-M Therapy Development - Recent research from the University of Sydney introduced CAR-M therapy, which uniquely transforms immune responses into immunosuppressive responses when triggered by inflammatory cytokines [7]. - The CAR-M design includes an extracellular domain that binds to tumor necrosis factor (TNF) and an intracellular domain that activates anti-inflammatory responses, programming macrophages to exhibit M2-like functions [7][10]. Group 3: Efficacy in Animal Models - CAR-M therapy demonstrated efficacy in both acute and chronic inflammatory disease models in mice, showing a transition to an anti-inflammatory phenotype in inflamed kidneys and improving kidney function and structure [8][10]. - In models of kidney ischemia-reperfusion injury, CAR-M cells effectively reduced tissue damage and maintained their anti-inflammatory phenotype in the presence of high TNF levels [8][10].