Establishing human immune system mice: application, opportunity, and challenges

Human immune system (HIS) models offer a promising solution to bridge clinical trial by providing a more functional platform in studying disease mechanisms and evaluating therapeutic responses. This Review provides an overview of various strains of immunodeficient mice used for human immune cell development and their current applications in disease modeling. We highlight the utility of single-cell RNA sequencing in HIS mice as a powerful approach for identifying drug targets and elucidating cellular mechanisms. Furthermore, we discuss four major challenges in HIS model establishment and summarize recent advancements aimed at enhancing human immune cell development. Finally, we present preclinical examples of HIS mice as disease platforms supporting clinical trials, illustrating their role as essential tools for drug development.