As people age, the capacity of their immune system deteriorates; T cell populations decrease and cannot react as quickly to pathogens. New research now shows that it is possible to reverse this with an innovative approach.
Specifically, the study in mice reveals that mRNA (messenger) technology can be used to transform the liver into a temporary source of important regulatory factors of the immune system that are lost naturally during aging.
This restores the formation of new immune cells, allowing aged animals to once again develop robust immune responses and effectively fight tumors.
“If we can restore something as essential as the immune system, hopefully we can help people stay disease-free for longer,” says Feng Zhang of the Massachusetts Institute of Technology (MIT) in the United States.
In addition to MIT, the Broad Institute, also in the United States, the German Cancer Research Center and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine are participating in the work. The details are published in the journal Nature.
The thymus and loss of function
The thymus, a small organ located in front of the heart, plays a critical role in the development and maturation of T cells. It also secretes cytokines and growth factors that help these cells survive.
However, starting in early adulthood, this begins to shrink, in a process known as thymic involution, which leads to a decrease in the production of new T cells; At approximately 75 years of age it is essentially inoperative.
In the new approach, the researchers wanted to see if they could create a temporary “factory” in the body that generated the T cell-stimulating signals that the thymus normally produces.
For this they chose the liver, which has a great capacity to produce proteins, even in old age, and it is easier to administer mRNA than to most organs. Additionally, all blood circulating through the body has to pass through it, including T cells.
To create their factory, the researchers identified three immune signals that are important for the maturation of T cells, explain separate statements from MIT and the German Cancer Center.
They encoded these three factors into mRNA sequences that could be delivered via lipid nanoparticles. When injected into the bloodstream, these particles accumulate in the liver and the mRNA is taken up by hepatocytes, which begin making the proteins encoded by the mRNA.
Beneficial effects
Tests on mice revealed beneficial effects. First, the researchers injected the mRNA particles into 18-month-old rodents, equivalent to humans in their 50s.
Following treatment, T cell populations showed a significant increase in size and function.
They then checked whether this could improve the animals’ response to vaccination. They vaccinated the mice with ovalbumin, a protein present in egg white that is commonly used to study how the immune system responds to a specific antigen.
In 18-month-old mice that received mRNA treatment before vaccination, the team found that the population of ovalbumin-specific cytotoxic T cells doubled, compared to those that did not receive mRNA therapy.
The team now plans to study this in other animal models and identify additional signaling factors that may improve immune system function. They also hope to look at how the treatment affects other immune cells, including B cells.
With information from EFE.
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