CAMBRIDGE, Mass., December 28, 2023 — Scientists have discovered a way to temporarily boost the immune system’s ability to fight off age-related decline, offering a potential path toward healthier aging. The innovative approach, developed by researchers at MIT and the Broad Institute, essentially reprograms liver cells to strengthen T cell performance—the very cells that often become sluggish with age.
Revving Up Immunity: A New Strategy for Healthy Aging
Table of Contents
A novel method to rejuvenate immune cells shows promise in mice, potentially paving the way for treatments that could help people stay healthier for longer.
- As we age, the thymus—the organ responsible for T cell maturation—shrinks, leading to a decline in immune function.
- Researchers have successfully used mRNA technology to temporarily turn liver cells into “factories” that produce key signals for T cell development.
- In mice, this treatment led to increased T cell populations, improved vaccine responses, and enhanced cancer immunotherapy effectiveness.
- The strategy avoids the harmful side effects associated with earlier attempts to boost immunity through direct T cell growth factor delivery.
What causes the immune system to weaken as we get older? The immune system’s decline is largely linked to the shrinking of the thymus, an organ crucial for developing a diverse and effective army of T cells. Beginning in early adulthood, this process, called thymic involution, reduces the body’s ability to produce new T cells. By around age 75, the thymus is largely nonfunctional, leaving older adults more vulnerable to infections.
The Thymus: The Immune System’s Training Ground
The thymus, located in front of the heart, isn’t just about quantity; it’s about quality. Within its walls, immature T cells undergo a rigorous “checkpoint” process, ensuring a diverse range of cells capable of recognizing and fighting off various threats. The thymus also releases vital cytokines and growth factors that support T cell survival.
“As we get older, the immune system begins to decline,” explained Mirco Friedrich, the lead author of the study. “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.”
A Liver-Based Solution Powered by mRNA
Previous attempts to rejuvenate the immune system by directly delivering T cell growth factors often resulted in unwanted side effects. Other researchers have explored transplanting stem cells to rebuild thymus tissue. The MIT team, however, took a different tack: could they prompt the body to create a temporary “factory” mimicking the thymus’s essential functions?
“Our approach is more of a synthetic approach,” said Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, and senior author of the study. “We’re engineering the body to mimic thymic factor secretion.”
The liver proved to be an ideal location for this temporary factory. It consistently produces large amounts of protein, even in older individuals. Delivering mRNA to the liver is relatively straightforward, and its central role in blood circulation ensures that immune-supporting signals reach T cells efficiently.
The researchers selected three key immune cues – DLL1, FLT-3, and IL-7 – involved in T cell maturation. They encoded these factors into mRNA and packaged them into lipid nanoparticles. Once injected, these nanoparticles deliver their cargo to liver cells, instructing them to produce the crucial proteins.
Promising Results in Mice
Experiments with 18-month-old mice (roughly equivalent to humans in their 50s) showed significant improvements. The team administered repeated doses of the mRNA over four weeks to maintain consistent production of the immune-boosting factors. The result? A substantial increase in both the number and function of T cells.
Vaccine responses also improved. Mice vaccinated with ovalbumin (a common antigen used in immune studies) after receiving the mRNA treatment exhibited double the number of cytotoxic T cells targeting the protein compared to untreated mice.
Perhaps most encouragingly, the treatment enhanced the effectiveness of cancer immunotherapy. Mice treated with both the mRNA and a checkpoint inhibitor drug (targeting PD-L1 to unleash T cell attacks on tumors) showed significantly higher survival rates and lived longer than those receiving the drug alone.
“If we can restore something essential like the immune system, hopefully we can help people stay free of disease for a longer span of their life,” Zhang stated.
The researchers emphasized that all three factors—DLL1, FLT-3, and IL-7—were essential for the observed improvements. Future research will focus on testing the approach in additional animal models, identifying further signaling factors to enhance immune function, and investigating the treatment’s impact on other immune cells, including B cells.
