3. Is IL-10 a master controller of the immune response? What regulates the regulator?
One of the key cytokines that mediates immune balance is one called IL-10. We would like to know what controls IL-10 production, and what affects IL-10's impact - in 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.