RNA binding proteins help T cells pick their weapons before battle


Date:
April 27, 2022
Source:
Babraham Institute
Summary:
Researchers have identified key drivers of T cell development
which promote resilience to influenza virus infection.



FULL STORY ========================================================================== Scientists at the Babraham Institute have shown that two RNA binding
proteins hold the key to a stronger immune response to influenza in
mice. Their findings, published today in Nature Communications, 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.


========================================================================== Researchers 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, those lacking the 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 "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."
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.

"Going forward we want to investigate how the absence of RNA binding
proteins affects the formation of immune memory and whether the enhanced cytotoxicity acquired early in the response is imprinted and maintained
in the memory phase." 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 program is established early
after T cell activation.


========================================================================== Story Source: Materials provided by Babraham_Institute. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Georg Petkau, Twm J. Mitchell, Krishnendu Chakraborty, Sarah
E. Bell,
Vanessa D'Angeli, Louise Matheson, David J. Turner, Alexander
Saveliev, Ozge Gizlenci, Fiamma Salerno, Peter D. Katsikis, Martin
Turner. The timing of differentiation and potency of CD8 effector
function is set by RNA binding proteins. Nature Communications,
2022; 13 (1) DOI: 10.1038/ s41467-022-29979-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220427115805.htm

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