Macrophage plasticity: signaling pathways, tissue repair, and regeneration

  • MedComm (2020). 2024 Aug 1;5(8):e658. doi: 10.1002/mco2.658.
Lingfeng Yan  1  2 ,  Jue Wang  1  2 ,  Xin Cai  1  2 ,  Yih-Cherng Liou  3  4 ,  Han-Ming Shen  5 ,  Jianlei Hao  6  7 ,  Canhua Huang  8 ,  Gaoxing Luo  1  2 ,  Weifeng He  1  2
Affiliations
  • 1. 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.
  • 2. Chongqing Key Laboratory for Wound Damage Repair and Regeneration Chongqing China.
  • 3. Department of Biological Sciences Faculty of Science National University of Singapore Singapore Singapore.
  • 4. National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering National University of Singapore Singapore Singapore.
  • 5. Faculty of Health Sciences University of Macau Macau China.
  • 6. 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.
  • 7. The Biomedical Translational Research Institute Faculty of Medical Science Jinan University Guangzhou Guangdong China.
  • 8. 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.
PMID: 39092292 DOI: 10.1002/mco2.658
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.

Keywords
epigenetic regulation; macrophages; plasticity; signaling pathways; tissue repair.