Metabolic Regulation of the Th2 Response

点击翻译按钮获取中文摘要

Our immune system is our principal defence against infection, but it is a double-edged sword. Inappropriate or over-exuberant immune responses can be as harmful as no response at all. Th2 immunity is a type of immune response that is associated with intestinal worm infections. It causes swelling, muscle contraction and an increase in the production of watery mucus, all of which contribute to flushing out the pathogen. However, the same Th2 response is also associated with allergies and asthma, and in these contexts the same hallmarks of Th2 immunity are damaging; they can even be fatal. Tissue swelling and watery mucus are behind many of the classic symptoms of hay fever, for example, and deeper in the lungs the same processes are responsible for many, severe asthma attacks. At the moment, our best treatment strategies for Th2-mediated diseases are drugs that cause generalised suppression of the whole immune system, like corticosteroids. Approaches that would enable us to fine-tune the Th2 response, selectively, would be a significant advance. Our aim in this project is to understand the cell biology behind the Th2 response and to identify key pathways that support or suppress Th2 development, so that in the future we can manipulate these pathways to control Th2 immunity. The particular pathways that we focus on are metabolic pathways, ones controlling how cells use energy to function. Recent evidence suggests that the activation of immune cells is associated with a dramatic change in their energy usage, as the activated cells begin to burn sugar in a frenetic attempt to fuel their rapid proliferation and increased function. The purpose of this project is to assess whether it is possible to use access to particular energy sources as a method of manipulating the function of immune cells. Our hypothesis is that the cells that participate in a Th2 response, such as one against a parasitic worm infection, are less reliant on sugar than the cells involved in an immune response that defends against a virus, for example. We propose that altering the immune system's patterns of energy use could determine the type of immune response that dominates, and hence whether the pathogen or the person will thrive or die. We anticipate that the data we produce and the new understanding we provide will not only accelerate the work of other scientists seeking to understand disease processes in infections, but will also benefit our colleagues in biotech and pharmaceutical industry who will move this information forward into drugs and therapeutic interventions. Our aim is that the progress we make will lead to targeted interventions in Th2 immunity and new therapies both for intestinal worm infections, and for allergies and asthma. Our work may also support policy makers and non-governmental organisations who promote action to achieve the best possible advancement in global health.