Researchers at The University of Texas Health Science Center at San Antonio have achieved a groundbreaking milestone by developing TruHuX, the world's first mouse model with a fully functional human immune system, marking a significant advancement in immunological and microbiological research. Advancing Human Immunology With TruHuX Mice
Unlike traditional mouse models, TruHuX boasts key human immune components such as lymph nodes, germinal centers, and thymus human epithelial cells. It also contains human T and B lymphocytes, memory B lymphocytes, and plasma cells capable of producing specific antibodies and autoantibodies mirroring those in humans. The model also hosts a human-like gut microbiome, enhancing its relevance for studying immune responses and diseases. This innovative approach paves the way for studying human diseases and testing therapies more accurately and ethically, potentially reducing reliance on non-human primates in research. Paolo Casali, MD, the University of Texas Ashbel Smith Professor and Distinguished Research Professor, explained that THX mice utilize estrogen activity to bolster human stem cell and immune cell development, enhancing antibody responses. Unraveling Immune Complexity in TruHuX Mice
The latest research revealed that these mice exhibit a broad range of human B cell and T cell antigen receptors, enabling them to produce sophisticated antibody responses through processes like somatic hypermutation and class-switch recombination. They can develop autoimmune responses similar to lupus after pristane injection. THX mice use estrogen activity to support human immune cell development and antibody maturation, offering a strong foundation for studying the human immune system and advancing human vaccines and treatments. Building on the success of the THX model, Casali's team is investigating these mice's response to SARS-CoV-2 (COVID-19) infection both systemically and locally, as well as human memory B cells, their reliance on the nuclear receptor RORα for formation, and the factors affecting RORα expression and dysregulation. Researchers are delving into epigenetic mechanisms governing the production of human plasma cells, vital for producing antibodies rapidly in response to pathogens or cancer cells. In the realm of biomedical innovation, TruHuX mice serve as a bridge between human biology and experimental exploration, opening new horizons in the pursuit of healthier futures.