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

放射治疗是头颈癌患者的救命疗法。虽然放射治疗在治疗癌症方面通常很成功，但严重的副作用是损害肿瘤附近的健康组织，包括唾液腺。这种组织损伤会导致唾液分泌能力下降（一种被称为口干或口干症的情况），从而导致进食、说话和睡眠困难。此外，它还会导致蛀牙和口腔健康问题。因此，放射治疗的副作用会对患者的生活质量产生不利影响。现有的治疗口干症的方法只能短期缓解，因此需要开发更好、更有效的治疗方法。一种促进受损唾液腺修复和再生的治疗方法是理想的，然而，由于对损伤后唾液腺中发生的修复和再生过程的不完全了解，这种方法目前受到阻碍。我们知道唾液腺周围的神经在需要的时候对分泌唾液很重要。我们还知道，神经可以向其他唾液腺细胞发送信号，帮助损伤或炎症后的组织修复和再生。放射治疗也会导致唾液腺中免疫细胞发生重大变化。巨噬细胞是唾液腺中最丰富的免疫细胞，长期以来被认为在许多不同器官的修复和再生中起着关键作用，但它们在损伤的唾液腺中发挥的确切作用尚不清楚。在初步的实验中，我们已经表明巨噬细胞和神经在唾液腺中彼此密切相关，但它们是否以及如何沟通以促进再生从未被研究过。在这个项目中，我们将研究巨噬细胞和神经是否通过交流促进唾液腺的修复和再生。具体来说，我们将确定如果巨噬细胞被移除，神经的存在和行为会发生什么变化。总的来说，这将告诉我们在唾液腺再生过程中神经和巨噬细胞是否协同工作，以及我们是否可以改善这种沟通以获得更好的再生。

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.