As people grow older, the immune system weakens, making the body more susceptible to infections and disease. Scientists have now reported a potential breakthrough that could help restore a vital part of immune function later in life. Researchers at the Broad Institute of MIT and Harvard have identified a way to revive the activity of the thymus, a small organ near the heart responsible for producing T cells, which play a key role in defending the body against cancer and infections. In experiments on mice, the team successfully reprogrammed a portion of the liver to act like a thymus, triggering signals that renewed T-cell production even after the thymus had begun to shrink with age.
"If we can restore something as essential as the immune system, we may help people remain disease-free for longer," said Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT. Zhang, who holds multiple roles across MIT, the Broad Institute, and the Howard Hughes Medical Institute, is the senior author of the study. Former MIT postdoctoral researcher Mirco Friedrich led the research, which was published in Nature in December 2025.
The thymus, located in front of the heart, is vital for producing and training T cells that protect the body from disease. It releases signals that support T-cell survival. However, from early adulthood the thymus gradually shrinks, a process called thymic involution, sharply reducing new T-cell production by old age.
"As we get older, the immune system begins to decline. We wanted to think about how can we maintain this kind of immune protection for a longer period of time, and that's what led us to think about what we can do to boost immunity," Friedrich says.
Earlier efforts to rejuvenate the immune system focused on injecting T-cell growth factors or using stem cell transplants, approaches that can carry risks or face technical limits. The MIT team instead pursued a synthetic strategy, aiming to temporarily recreate thymus-like signals inside the body. They chose the liver as a “factory” because of its strong protein-producing ability, ease of mRNA delivery, and central role in blood circulation. Researchers packaged three key immune factors, DLL1, FLT-3 and IL-7, into mRNA delivered via lipid nanoparticles. Once absorbed by liver cells, these instructions prompted the production of signals that drive immature T cells to mature and function effectively.
