Scientists at the Babraham Institute have demonstrated that two RNA binding proteins have the potential to increase immunity to influenza in mice. These findings, published today in Nature Communications, demonstrate that the absence of these proteins changes the potential of T cells that arise at the start of an infection. Further research might have implications for therapies that harness the immune system and for vaccination design.
Researchers from the Turner laboratory focused on the activity of the RNA binding proteins ZFP36 and ZFP36L1. By studying mice lacking these RNA binding proteins, they were able to show that their absence in T cells during the initial phase of a viral infection leads to a superior cytotoxic immune response.
When the researchers investigated infected mice with influenza, the ones lacking their RNA binding proteins in T cells showed signs of improvement in treatment of the infection more effective than those with the proteins present. They also transacted cells that lacking ZFP36 and ZFP36L1 into normal mice, revealing that even small quantities of transferred T cells provided the same advantage when dealing with an influenza infection.
The results of the survey were incredible, according to Dr Georg Petkau, a postdoctoral researcher. 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 result in signs of disease or tissue damage, which is often a logical consequence of overt cytotoxicity during an immune response.
The findings suggest that the absence of negative knock on effects might result in rapid viral clearance and might result in a quicker resolution of infection in young mice. It would be interesting to see whether an extensive accumulation of memory cells that show enhanced cytotoxicity in absence of RNA binding proteins would become potentially dangerous with age. Understanding how these RNA binding proteins might thus also be beneficial for autoimmune disease formation in elderly individuals.
The priming of the immune response once a pathogen is discovered is a critical step which significantly alters the course of an immune response; it is the point at which immune cells select their weapons before they begin to battle the infection. This is through RNA binding proteins. The researchers hope to inform how we approach vaccination design and cell therapies.
The study will focus on how the absence of RNA binding proteins affects immune memory development, and whether the superior cytotoxic traits acquired early in the response are epigenetically imprinted and maintained in the memory phase. Dr Martin Turner, the researchers'' head of the Immunology research programme, believes that this method is soon established by research on abnormal changes in the epigenome.