Dissecting the cellular and molecular basis of macrophage-nerve crosstalk in the salivary gland in health and regeneration

点击翻译按钮获取中文摘要

Radiotherapy is a life-saving treatment for those with head and neck cancer. Although radiotherapy is very often successful in treating the cancer, a serious side-effect is damage to healthy tissue near the tumour(s), including the salivary glands. This tissue damage results in reduced ability to produce saliva (a condition known as dry mouth or xerostomia), which leads to difficulties with eating, speaking and sleeping. Furthermore, it causes tooth decay and oral health problems. Thus, the side-effects of radiotherapy adversely affect a patient's quality of life. Existing treatments for xerostomia only give short-term relief and therefore there is a need to develop better, more effective treatments. A treatment that promotes the damaged salivary gland to repair and regenerate would be ideal, however this approach is currently prevented by an incomplete understanding of the repair and regeneration processes that occur in the salivary gland following injury. We do know that the nerves surrounding the salivary glands are important for producing saliva when it is required. We also know that nerves can send signals to other salivary gland cells to help repair and regeneration of the tissue following injury or inflammation. Radiation treatment also leads to major changes in the immune cells present in the salivary gland. Macrophages are the most abundant immune cell in the salivary gland and they have long been considered key players in the repair and regeneration of many different organs, yet the exact roles they perform in the injured salivary gland remain unclear. In preliminary experiments we have shown that macrophages and nerves closely associate with one another in the salivary gland, but if and how they communicate to promote regeneration has never been studied. In this project we will investigate whether macrophages and nerves communicate to promote salivary gland repair and regeneration. Specifically, we will determine what happens to the presence and behaviour of nerves if macrophages are removed. Collectively, this will tell us if nerves and macrophages work together during regeneration of the salivary gland, and if we can improve this communication to get better regeneration.