T cells were helped by RNA binding proteins to pick their weapons for battle

T cells were helped by RNA binding proteins to pick their weapons for battle ...

Scientists at the Babraham Institute have shown that two RNA binding proteins have the potential to strengthen immunity to influenza in mice. Their findings, published today in Nature Communications, reveal that the absence of these proteins changes the ability 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 planning.

Researchers from the Turner lab focused on the activity of ZFP36 and ZFP36L1, which are RNA binding proteins. By using mice with 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.

The ones lacking their RNA binding proteins in T cells were shown to be capable of combating the infection more effectively than those with the proteins present. They also transferred cells that lacked ZFP36 and ZFP36L1 into normal mice, and found that even a small number of transferred T cells provided the same advantage when dealing with an influenza infection.

The results of the study were remarkable, according to Dr Georg Petkau, a postdoctoral researcher. One striking conclusion of our study is that although the absence of RNA binding proteins in T cells results in stable accelerated differentiation and increased 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.

The findings suggest that the absence of negative effects might result in faster viral clearance and might result in a faster resolution of infection in young mice. It might be interesting to see whether a large accumulation of memory cells with enhanced cytotoxicity in absence of RNA binding proteins might become potentially dangerous with age. However, understanding how these RNA binding proteins may thus affect 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; this is the point at which immune cells must choose their weapons before they start to fight the infection. This is done by RNA binding proteins, which bind signals to activate T cells. Researchers hope to improve the way we approach vaccine design and cell therapies.

Going forward, we want to investigate how the absence of RNA binding proteins affects immune memory and whether the superior cytotoxic traits acquired early in the response are epigenetically imprinted and maintained in the memory phase.

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