As the years pass, colds drag on, vaccines protect less well and cancers become more difficult to contain. Doctors see this as the sign of a tired immune system, with no easy way to get it back up to speed. Researchers from MIT however, believe they have found an astonishing lead in mice.
In a study published in December 2025 in Naturethey describe how to temporarily program liver cells to produce signals capable of supporting
T lymphocytes. In aged animals, this approach revived responses to vaccination andimmunotherapy anticancer. What to talk about, cautiously, about immune rejuvenation.
Why our immunity ages
At the heart of this decline is the
thymusa small organ in front of the heart where T cells are born and mature which track viruses, bacteria and tumors. From the start of adulthood, it shrinks, a phenomenon of “thymic involution”, and produces fewer and fewer new lymphocytes.
This defense factory becomes almost silent: around the age of 75, the thymus is considered almost non-functional. “Over the years, the immune system begins to decline. We wanted to think about how to maintain this type of immune protection for longer, and that’s what led us to consider what we can do to boost immunity,” explained Mirco Friedrich, a former postdoctoral fellow at MIT.
Transforming the liver into a mini immune factory
To circumvent this aging of the thymus, the team of
Broad Institute of MIT and Harvard had an idea: externalize its signals in the liver, an organ that produces a lot of proteins. “Our approach is rather a synthetic approach“, explains Feng Zhang. “We program the body to mimic the secretion of thymic factors“.
The method is based onMessenger RNA
encapsulated in lipid nanoparticles, similar in principle to that of mRNA vaccines but with other genes. Once injected, this mRNA is taken up by liver cells, which produce three key proteins for the survival and maturation of T cells: DLL1, FLT-3L and IL-7. The expression is transient, which requires repeated injections over four weeks in the 18-month-old mice used in the study, the equivalent for a fifty-year-old human being.
Promising results, but still very preliminary
In treated mice, the number and diversity of T lymphocytes increased.
The scientists then explored whether the treatment could optimize vaccine response in animals. They administered a vaccine based on ovalbumin, an egg white protein often used to analyze the immune response to a specific antigen, to mice. In 18-month-old rodents that received mRNA treatment before vaccination, they observed a doubling of the population of cytotoxic T lymphocytes specific to ovalbumin, compared to mice of the same age that did not receive this treatment.
Researchers also found that mRNA treatment could intensify the immune response to cancer immunotherapy. They administered this treatment to 18-month-old mice, which were implanted with tumors, and which were then treated with an immune checkpoint inhibitor. This drug, targeting the PD-L1 protein, is designed to release the brakes on the immune system and encourage T cells to attack cancer cells. Mice that received the treatment showed significantly higher survival rates and prolonged life expectancy compared to those that only received the checkpoint inhibitor without the mRNA treatment.
The researchers concluded that all three factors were essential to induce this immune stimulation; none of them alone could cover all aspects. They now plan to explore the treatment in other animal models and discover other signaling factors that could further improve the immune system. They also want to examine the impact of the treatment on other immune cells, such as B cells.
The authors plan further animal trials and want to analyze the effect on other immune cells, such as B lymphocytes.”If we can restore something essential like the immune system, we can hopefully help people stay disease-free for a longer part of their lives” Feng Zhang said.