Published on: Dec 17, 2025
As people age, immune function gradually weakens. T-cell numbers decline, and their ability to respond rapidly to pathogens diminishes, increasing vulnerability to infections.
To address this challenge, researchers at MIT and the Broad Institute have developed a strategy that temporarily reprograms liver cells to enhance T-cell function. This approach compensates for age-related deterioration of the thymus—the organ responsible for T-cell maturation.
By using mRNA to deliver three key signals that normally support T-cell development and survival, the researchers successfully rejuvenated the immune systems of aged mice. Treated mice exhibited larger and more diverse T-cell populations following vaccination and showed improved responses to cancer immunotherapy.
The researchers suggest that, if adapted for clinical use, this strategy could help support healthier aging by restoring immune resilience.
“If we can restore something as fundamental as immune function, we may be able to help people remain disease-free for a longer portion of their lives,” says Feng Zhang, senior author of the study.
The thymus plays a crucial role in shaping a diverse and functional T-cell population, but it begins shrinking in early adulthood—a process known as thymic involution. By around age 75, its activity is greatly reduced, leading to fewer newly generated T cells.
Rather than attempting to regenerate the thymus directly, the researchers took a synthetic biology approach: engineering the body to temporarily produce thymus-like signals elsewhere. They selected the liver as an ideal site due to its high protein-production capacity, ease of mRNA delivery, and constant exposure to circulating blood cells.
Using lipid nanoparticles, the team delivered mRNA encoding three immune factors—DLL1, FLT-3, and IL-7—into liver cells. These cells then acted as a short-term “factory,” producing signals that support T-cell maturation and survival.
In aged mice receiving repeated treatments over four weeks, T-cell populations increased significantly in both size and function. When vaccinated, treated mice generated roughly double the number of antigen-specific cytotoxic T cells compared with untreated peers.
The approach also enhanced cancer immunotherapy outcomes. Aged mice receiving both the mRNA treatment and a checkpoint inhibitor showed improved survival and longer lifespan than those receiving immunotherapy alone.
All three immune factors were required to achieve the full rejuvenating effect. The researchers plan to explore additional signaling combinations, test the approach in other animal models, and study its effects on other immune cells such as B cells.
Source: https://news.mit.edu/2025/new-study-suggests-way-rejuvenate-immune-system-1217
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