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A new study from researchers at MIT and the Broad Institute suggests a promising way to rejuvenate the ageing immune system by temporarily reprogramming the liver to support T-cell development. As people get older, the thymus — the organ where T cells mature — gradually shrinks, leading to fewer and less responsive T cells and greater vulnerability to infections and cancer. To bypass this decline, the team created a synthetic workaround that mimics key functions of the thymus elsewhere in the body.
Led by Mirco Friedrich and published in Nature, the study used mRNA packaged in lipid nanoparticles to deliver instructions for three immune-boosting factors (DLL1, FLT-3, and IL-7) directly to liver cells in mice. The liver then acted as a temporary “factory,” producing signals that help immature T cells survive and mature. In older mice, this approach significantly increased the size and diversity of T-cell populations, effectively restoring more youthful immune function.
The benefits were striking: treated mice mounted much stronger responses to vaccination, with antigen-specific killer T cells doubling in number, and they responded better to cancer immunotherapy, showing higher survival rates when combined with checkpoint inhibitor drugs. Senior author Feng Zhang says the long-term goal is to help people stay healthier for longer by restoring essential immune functions. While the work is still at the animal stage, the researchers hope to test the approach in other models and explore whether it could one day help counter immune ageing in humans.
