Tiwari Satish Kumar, Wong Wei Jie, Moreira Marco, Pasqualini Claudia, Ginhoux Florent
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Rev Immunol. 2025 Feb;25(2):108-124. doi: 10.1038/s41577-024-01081-x. Epub 2024 Sep 27.
Macrophages are innate immune cells that are present in essentially all tissues, where they have vital roles in tissue development, homeostasis and pathogenesis. The importance of macrophages in tissue function is reflected by their association with various human diseases, and studying macrophage functions in both homeostasis and pathological tissue settings is a promising avenue for new targeted therapies that will improve human health. The ability to generate macrophages from induced pluripotent stem (iPS) cells has revolutionized macrophage biology, with the generation of iPS cell-derived macrophages (iMacs) providing unlimited access to genotype-specific cells that can be used to model various human diseases involving macrophage dysregulation. Such disease modelling is achieved by generating iPS cells from patient-derived cells carrying disease-related mutations or by introducing mutations into iPS cells from healthy donors using CRISPR-Cas9 technology. These iMacs that carry disease-related mutations can be used to study the aetiology of the particular disease in vitro. To achieve more physiological relevance, iMacs can be co-cultured in 2D systems with iPS cell-derived cells or in 3D systems with iPS cell-derived organoids. Here, we discuss the studies that have attempted to model various human diseases using iMacs, highlighting how these have advanced our knowledge about the role of macrophages in health and disease.
巨噬细胞是先天性免疫细胞，几乎存在于所有组织中，在组织发育、体内平衡和发病机制中发挥着至关重要的作用。巨噬细胞与多种人类疾病相关，这反映了其在组织功能中的重要性。在体内平衡和病理组织环境中研究巨噬细胞功能，是开发有望改善人类健康的新型靶向治疗方法的一个有前景的途径。从诱导多能干细胞（iPS细胞）生成巨噬细胞的能力彻底改变了巨噬细胞生物学，iPS细胞衍生的巨噬细胞（iMacs）的产生为获取特定基因型细胞提供了无限途径，这些细胞可用于模拟各种涉及巨噬细胞失调的人类疾病。通过从携带疾病相关突变的患者来源细胞生成iPS细胞，或使用CRISPR-Cas9技术将突变引入健康供体的iPS细胞来实现这种疾病建模。这些携带疾病相关突变的iMacs可用于体外研究特定疾病的病因。为了实现更高的生理相关性，iMacs可以在二维系统中与iPS细胞衍生的细胞共培养，或在三维系统中与iPS细胞衍生的类器官共培养。在这里，我们讨论了试图使用iMacs模拟各种人类疾病的研究，强调了这些研究如何推进了我们对巨噬细胞在健康和疾病中作用的认识。
