接受头颈癌放射治疗的人的唾液腺经常受损，导致慢性口干。这会对他们的健康和生活质量产生不利影响，而对此没有再生疗法。巨噬细胞是唾液腺中的主要免疫细胞，由于其驱动组织修复的无与伦比的能力而成为有吸引力的治疗靶点。然而，巨噬细胞在唾液腺稳态中的性质和作用以及它们如何促进损伤后的组织修复尚不清楚。在这里，我们发现成人唾液腺中至少存在两个表型和转录上不同的 CX3CR1 巨噬细胞群，它们占据了解剖学上不同的生态位。 CD11c CD206-CD163-巨噬细胞通常与腺上皮相关，而CD11c-CD206 CD163-巨噬细胞与血管和神经相关。使用一套互补的命运图谱系统，我们发现唾液腺巨噬细胞的个体发育和组成随着年龄的增长而发生高度动态的变化。利用辐射诱导唾液腺损伤的体内模型，结合遗传或抗体介导的巨噬细胞耗竭，我们证明了巨噬细胞在清除 DNA 损伤细胞中的重要作用。此外，我们发现上皮相关巨噬细胞对于辐射引起的损伤后的有效组织修复和腺体功能是不可或缺的，其消耗会导致唾液产生减少。因此，我们的数据为探索操纵巨噬细胞促进组织修复的治疗潜力提供了强有力的案例，从而最大限度地减少放射治疗后的唾液腺功能障碍。

The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis and how they may contribute to tissue repair after injury are not well understood. Here, we show that at least two phenotypically and transcriptionally distinct CX3CR1+ macrophage populations are present in the adult salivary gland, which occupy anatomically distinct niches. CD11c+CD206-CD163- macrophages typically associate with gland epithelium, whereas CD11c-CD206+CD163+ macrophages associate with blood vessels and nerves. Using a suite of complementary fate mapping systems, we show that there are highly dynamic changes in the ontogeny and composition of salivary gland macrophages with age. Using an in vivo model of radiation-induced salivary gland injury combined with genetic or antibody-mediated depletion of macrophages, we demonstrate an essential role for macrophages in clearance of cells with DNA damage. Furthermore, we show that epithelial-associated macrophages are indispensable for effective tissue repair and gland function after radiation-induced injury, with their depletion resulting in reduced saliva production. Our data, therefore, provide a strong case for exploring the therapeutic potential of manipulating macrophages to promote tissue repair and thus minimize salivary gland dysfunction after radiotherapy.