Macrophage plasticity: signaling pathways, tissue repair, and regeneration
Lingfeng Yan,
Jue Wang,
Xin Cai,
Yih‐Cherng Liou,
Han‐Ming Shen,
Jianlei Hao,
Canhua Huang,
Gaoxing Luo,
Weifeng He
Affiliations
Lingfeng Yan
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China
Jue Wang
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China
Xin Cai
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China
Yih‐Cherng Liou
Department of Biological Sciences Faculty of Science National University of Singapore Singapore Singapore
Han‐Ming Shen
Faculty of Health Sciences University of Macau Macau China
Jianlei Hao
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Institute of Translational Medicine Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University) Jinan University Zhuhai Guangdong China
Canhua Huang
State Key Laboratory of Biotherapy and Cancer Center West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine Sichuan University, and Collaborative Innovation Center for Biotherapy Chengdu China
Gaoxing Luo
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China
Weifeng He
Institute of Burn Research State Key Laboratory of Trauma and Chemical Poisoning the First Affiliated Hospital of Army Medical University (the Third Military Medical University) Chongqing China
Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll‐like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.
