Two RNA binding proteins have been discovered to be the key to a greater immune reaction to influenza in mice, according to researchers at the Babraham Institute. Their observations, which were published in Nature Communications, show that the lack of these proteins alters the potency of T cells that develop early in an infection. Further study could have ramifications for immune-system-based therapeutics and vaccine development.
Turner lab researchers are interested in the activities of the RNA binding proteins ZFP36 and ZFP36L1. The scientists were able to demonstrate that the lack of these RNA binding proteins in T cells during the early stages of a viral infection results in a superior cytotoxic immune response by analyzing animals without these proteins.
When the mice were infected with influenza, the ones that did not have their RNA binding proteins in T cells showed symptoms of being able to fight the illness better than those who did. They also tested cells that lacked ZFP36 and ZFP36L1 in normal mice and discovered that very tiny numbers of transplanted T cells gave the same benefit in fighting influenza.
Their results were astounding, explains Dr Georg Petkau, a postdoctoral researcher who headed the work.
One striking observation of our study is that although the absence of RNA binding proteins in T cells results in stable accelerated differentiation and enhanced cytotoxicity, this does not lead to signs of disease or tissue damage, which is often a logical consequence of overt cytotoxicity during an immune response.”
Dr Georg Petkau, Postdoctoral Researcher, Babraham Institute
The absence of negative knock-on effects could be attributed to quicker antiviral therapy, which could be characterized by a faster resolution of infection in young mice, according to the researchers.
It would be worthwhile to explore if a big buildup of memory cells that display heightened cytotoxicity in the lack of RNA binding proteins becomes potentially harmful with age as a result of recurrent infections. Studying how these RNA binding proteins limit T cell activation could have ramifications for the development of autoimmune diseases in the elderly.
Once a pathogen is discovered, boosting the immune response is a vital phase that dramatically alters the nature of the immune response. It is the point at which immune cells decide how to modify the longevity and quality of the immune response to an attack. In a way, the T cells in this research must choose their weapons before they could even fight the virus, and RNA binding proteins help them do so.
Scientists seek to improve vaccine development and cell treatments by learning more about how the immune system encompasses data within hours of infection and how RNA binding proteins incorporate signals to activate T cells.
Going forward we want to investigate how the absence of RNA binding proteins affects the formation of immune memory and whether the superior cytotoxic traits acquired early in the response are epigenetically imprinted and maintained in the memory phase.”
Dr Martin Turner, Head, Immunology Research Program, Babraham Institute
As a result, the scientists will attempt to articulate their observations by looking at alterations in the epigenome to see how the persistent cytotoxic program is set up early after initiation.
Petkau, G., et al. (2022) The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins. Nature Communications. doi.org/10.1038/s41467-022-29979-x.