Grant: CIHR New Investigator

Our immune system is our chief defence against infection, but it is a double-edged sword. Inappropriate or over-exuberant immune responses can be harmful or even fatal. The optimal response is one that is strong enough to clear the pathogen but not so strong that it also kills the host, and I am working to understand how that balance is achieved. I study a family of signalling molecules known as cytokines, soluble messengers used by cells of the immune system to communicate with one another. It has been thought that cytokine signalling is tightly controlled in time and space, so that cytokines very precisely relay their message from one cell to another. The aim of this proposal is to find out whether cytokine signals also affect cells that are not the intended target. My hypothesis is that cytokine signalling can be indiscriminate, and that many cells not intending to participate in the immune response are nonetheless affected by the cytokine signals taking place around them. My prediction is that such indiscriminate cytokine signalling can alter the subsequent behaviour of these bystander cells. I will test my hypothesis using a series of transgenic mice that allow me to follow cytokine production and cytokine signalling as they happen, in a physiological immune system. My work will clarify a critical aspect of how cytokines control immune responses, and I anticipate that this knowledge will facilitate the development of new strategies for therapeutically manipulating immune responses.