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

剖析唾液腺巨噬细胞-神经串扰在健康和再生中的细胞和分子基础

• 批准号: MR/W004763/1
• 负责人: Calum Bain
• 金额: $ 25.38万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW004763%2F1
• 关键词: Dissecting; cellular; molecular; basis; macrophage

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.

放射治疗是一种挽救生命的治疗头颈部癌症。虽然放射疗法通常能成功治疗癌症，但严重的副作用是损害肿瘤附近的健康组织，包括唾液腺。这种组织损伤导致产生唾液的能力降低（一种称为口干或口腔干燥的疾病），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，放射治疗的副作用对患者的生活质量产生不利影响。现有的口干症治疗方法只能短期缓解，因此需要开发更好，更有效的治疗方法。促进受损唾液腺修复和再生的治疗将是理想的，然而这种方法目前由于对损伤后唾液腺中发生的修复和再生过程的不完全理解而受到阻碍。我们确实知道，唾液腺周围的神经在需要时对产生唾液很重要。我们还知道，神经可以向其他唾液腺细胞发送信号，以帮助修复和再生损伤或炎症后的组织。放射治疗也导致唾液腺中存在的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，长期以来一直被认为是许多不同器官修复和再生的关键参与者，但它们在受损唾液腺中的确切作用仍不清楚。在初步实验中，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交流以促进再生从未被研究过。在这个项目中，我们将调查是否巨噬细胞和神经沟通，以促进唾液腺修复和再生。具体来说，我们将确定如果去除巨噬细胞，神经的存在和行为会发生什么。总的来说，这将告诉我们神经和巨噬细胞是否在唾液腺再生过程中共同工作，以及我们是否可以改善这种沟通以获得更好的再生。

项目成果

CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury

• DOI: 10.1126/sciimmunol.add4374
• 发表时间: 2023-11
• 期刊: Science Immunology
• 影响因子: 24.8
• 作者: John G. McKendrick;Gareth-Rhys Jones;Sonia S. Elder;Erin Watson;W. T’Jonck;Ella Mercer;Marlene S. Maga

The role of salivary gland macrophages in infection, disease and repair.

唾液腺巨噬细胞在感染、疾病和修复中的作用。

• DOI: 10.1016/bs.ircmb.2022.02.001
• 发表时间: 2022
• 期刊: International review of cell and molecular biology
• 作者: McKendrick JG

CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration following radiation-induced injury

• DOI: 10.1101/2022.06.12.495803
• 发表时间: 2022-06
• 期刊: bioRxiv
• 作者: J. McKENDRICK;G. Jones;Sonia S. Elder;Ella Mercer;M. Magalhaes;C. Rocchi;L. Hegarty;A. L. Johnson-A