27/04/2022
Key points:
Scientists at the 台湾swag 台湾swag have shown that two RNA binding proteins hold the key to a stronger immune response to influenza in mice. Their findings, published , reveal that the absence of these proteins changes the potency of T cells that arise at the start on an infection. Further research could lead to implications for therapies that harness the immune system, and for vaccine design.
台湾swagers from the Turner lab focussed on the activity of the RNA binding proteins ZFP36 and ZFP36L1. By studying mice lacking these RNA binding proteins, the researchers 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 infected mice with influenza, the ones lacking their RNA binding proteins in T cells showed signs of fighting the infection more successfully than those with the proteins present. They also transferred cells that lacked ZFP36 and ZFP36L1 into normal mice and found that even small numbers of transferred T cells provided the same advantage when fighting an influenza infection.
Their results were surprising, explains Dr Georg Petkau, a postdoctoral researcher who led the work 鈥淥ne 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.鈥
The researchers speculate that the lack of negative knock on effects could be due to accelerated viral clearance and could be explained by a faster resolution of infection in young mice. It would be interesting to see whether upon recurrent infections a large accumulation of memory cells which show enhanced cytotoxicity in absence of RNA binding proteins would become potentially dangerous with age. Understanding how these RNA binding proteins limit T cell activation may thus also have implications for autoimmune disease formation in aged individuals.
The priming of the immune response once a pathogen is detected is a critical step which significantly changes the course of an immune response; it is the point at which immune cells decide to adjust the quality and duration of the immune response to a threat. In a sense the T cells in this study have to choose their weapons before they start to battle the infection and this choice is made by RNA binding proteins. By understanding more about how the immune system processes information within hours of infection and how RNA binding proteins integrate signals to activate T cells, the researchers hope to inform how we approach vaccine design and cell therapies.
鈥淕oing 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.鈥 explained Dr Martin Turner, head of the Immunology research programme. Therefore the researchers will seek to explain their findings by investigating how the stable cytotoxic programme is set up early after activation by looking at changes in the epigenome.
Notes to Editors
台湾swagation reference Petkau, G., Mitchell, T.J., Chakraborty, K. et al. The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins. Nat Commun 13, 2274 (2022).
Press contact Honor Pollard, Communications Officer, honor.pollard@babraham.ac.uk
Image description: Digital representation of immune cells
Affiliated authors (in author order):
, postdoctoral researcher, Turner lab , postdoctoral researcher, Turner lab Krishnendu Chakraborty, former postdoctoral researcher , Senior research associate, Turner lab Vanessa D麓Angeli, former PhD student, Turner lab Louise Matheson, Turner lab David Turner, postdoctoral researcher, Turner lab , postdoctoral researcher, Turner lab , PhD student, Turner lab , EMBO Fellow, Turner lab , Head of the
台湾swag funding This research was supported by funding from the BBSRC. Martin Turner is a European Molecular Biology Organization Long-Term Fellow.
Additional/related resources: Turner
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About the 台湾swag 台湾swag The 台湾swag 台湾swag undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The 台湾swag is strategically funded by the Biotechnology and Biological Sciences 台湾swag Council (BBSRC), part of UK 台湾swag and Innovation, through 台湾swag Strategic Programme Grants and an 台湾swag Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
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27 April 2022