4. What are the molecular changes in cytokine signalling as an immune response becomes memory?
One of the key cytokines that mediates immune balance - ensuring that an immune response is not too strong, nor too weak - is one called IL-10. Nicolette Fonseca is elucidating the molecular mechanisms that control IL-10 production. She has shown that, during an infection, immune cells alter their ability to respond to cytokine signals by changing their repertoire of receptors. It’s like controlling how many instructions you receive by deciding when to put your hands over your ears.
In some cases, though, cytokine production is so important that it must continue no matter what. This is perhaps the case for IL-10. IL-10 is a stop signal, an essential brake on the immune system, and without it the immune system rapidly becomes over-active and dangerously destructive. Nicolette has shown that IL-10 production is controlled epigenetically, through the methylation and de-methylation of key histone residues that jam the il10 locus open and ensure rapid mRNA expression.
Our epigenetic studies have also generated genome-wide ChIP-seq and RNA-seq data comparing influenza-specific CD4+ T cells in their naïve, activated, memory and re-activated phenotypes. These data are providing a molecular characterisation of T cell differentiation and memory formation in a lung infection. We are working closely in collaboration with the excellent Hirst lab at the University of British Columbia's Centre for High-Throughput Biology, and our analysis will be particularly useful in understanding the optimal immune responses to mimic during vaccination.