3. Immune balance, and the central role of IL-10
The optimal immune response is not always the strongest. A balance has to be struck between immune strength to clear the pathogen, and immune regulation to minimise collateral damage to the host. One of the key cytokines that mediates such balance is one called IL-10. We are working to understand what factors control IL-10 production, and also IL-10's impact. To do this, we are using a variety of infections, both in the gut and the lung.
One project is elucidating the molecular mechanisms that direct IL-10 production. We've 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. We've also shown that IL-10 production is controlled epigenetically, through the methylation and de-methylation of key histone residues that open the il10 locus and ensure rapid mRNA expression. We are now investigating the signals that initiate these epigenetic changes.
IL-10 is renown for its potent ability to restrain or stop immune responses, but in some circumstances it can play a very different role. In the context of a gut worm infection, we hypothesise that IL-10 is both pro-inflammatory and pro-repair, and our current studies are testing both possibilities.