The World’s First Mouse Model With A Fully Functional Human Immune System Has Been Developed

Researchers at The University of Texas Health Science Center in San Antonio have created the first mouse model of a human immune system that is fully functional. Known by the abbreviation TruHuX, which stands for “truly human” or THX, this novel model has a human-like gut microbiota that can produce certain antibody responses in addition to having a full human immune system.

The TruHuX mice contain key human immune components such as lymph nodes, germinal centers, thymus human epithelial cells, human T and B lymphocytes, memory B lymphocytes, and plasma cells. These elements produce highly specific antibodies and autoantibodies identical to those found in humans. Dr. Paolo Casali, Ashbel Smith Professor and Distinguished Research Professor at the University of Texas, emphasized the significance of leveraging estrogen activity to support human stem cell and immune cell differentiation. This enables the THX mice to serve as a platform for studying the human immune system, developing vaccines, and testing therapeutics.

Dr. Casali states that this discovery opens up new possibilities for in vivo research on humans, such as the creation of immunotherapeutics like cancer checkpoint inhibitors, vaccinations against bacterial and viral infections, and the modeling of different human diseases. These mice can develop mature T cell-dependent and T cell-independent antibody responses, and they display a variety of human B cell and T cell antigen receptor repertoires, according to study published in Nature. Interestingly, after receiving a pristane injection, the mice may also develop lupus autoimmunity.

The THX model opens possibilities for reducing reliance on non-human primates in immunological and microbiological biomedical research. Leveraging estrogen activity, these mice support the differentiation and maturation of human immune cells and antibody responses, providing a critical platform for studying human immune mechanisms and developing vaccines and therapeutics.

Currently, the Casali lab is investigating the in vivo human immune response to SARS-CoV-2 (COVID-19) at both systemic and local levels. They are also examining the role of nuclear receptor ROR? in the generation of human memory B lymphocytes and the epigenetic factors that mediate the production of human plasma cells, which are essential for generating antibodies against bacteria, viruses, or cancer cells.

Mice are commonly used in biological and biomedical research due to their small size, ease of handling, shared immune elements with humans, and susceptibility to genetic modification. The TruHuX model represents a significant advancement, offering new insights and opportunities in biomedical research.

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