巨噬细胞在发育、稳态和免疫中发挥着多样的作用。相应地，巨噬细胞功能异常参与了多种疾病的发生和进展，如2019冠状病毒病和动脉粥样硬化。巨噬细胞在不同条件下所产生的保护性或致病性效应很大程度上取决于它们的功能可塑性，该可塑性通过信号转导（如Janus激酶-信号转导子与转录激活因子、Wnt和Notch通路）受到环境刺激的调节。在过去的几十年里，人们逐渐揭示了巨噬细胞信号通路的分子机制，为疾病治疗提供了更多的替代治疗靶点。在这里，我们对巨噬细胞的基本生理进行概述，并详述了其内部的调控途径。我们还着重介绍了巨噬细胞在自身免疫、神经退行性、代谢性、传染性疾病和癌症的发病机制中扮演的关键角色，并关注针对信号通路成分和调节因子的调节策略方面的巨噬细胞靶向策略的进展。最后，我们讨论了巨噬细胞靶向治疗在临床应用中面临的挑战和可能的解决方案。我们希望这篇综述能为进一步研究针对巨噬细胞信号通路的治疗策略提供方向，从而提高疾病治疗的效果。© 2023 作者。MedComm由四川国际医疗交流促进会（SCIMEA）和约翰·威利与澳大利亚有限公司（John Wiley & Sons Australia, Ltd）出版。

Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved in the occurrence and progression of various diseases, such as coronavirus disease 2019 and atherosclerosis. The protective or pathogenic effect that macrophages exert in different conditions largely depends on their functional plasticity, which is regulated via signal transduction such as Janus kinase-signal transducer and activator of transcription, Wnt and Notch pathways, stimulated by environmental cues. Over the past few decades, the molecular mechanisms of signaling pathways in macrophages have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview of the basic physiology of macrophages and expound the regulatory pathways within them. We also address the crucial role macrophages play in the pathogenesis of diseases, including autoimmune, neurodegenerative, metabolic, infectious diseases, and cancer, with a focus on advances in macrophage-targeted strategies exploring modulation of components and regulators of signaling pathways. Last, we discuss the challenges and possible solutions of macrophage-targeted therapy in clinical applications. We hope that this comprehensive review will provide directions for further research on therapeutic strategies targeting macrophage signaling pathways, which are promising to improve the efficacy of disease treatment.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.