Roles of resident macrophages in salivary gland development, homeostasis, regeneration, and function restoration after radiotherapy

常驻巨噬细胞在放疗后唾液腺发育、稳态、再生和功能恢复中的作用

• 批准号: 10634722
• 负责人: Fei Liu
• 金额: $ 35.98万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634722
• 关键词: Address; Adult; Affect; Anti-Inflammatory Agents; Binding; Cells; Cessation of life; Complement 1q; Dendrites; Development; Duct (organ) structure; Embryo; Endothelial Cells; Epithelial Cells; Epithelium; Feasibility Studies; Functional Regeneration; Gene Expression; Gene Transfer; Goals; Growth Factor; Hand; Head and Neck Cancer; Homeostasis; Immune response; Impairment; Inflammation; Inflammatory; Infusion procedures; Interleukin-10; Interleukin-15; Kinetics; Knock-out; Knowledge; Ligation; Lymphoid Cell; Macrophage; Maintenance; Membrane; Molecular; Morphology; Mouse Strains; Mus; Natural regeneration; Outcome; Outcomes Research; Oxidative Stress; Patients; Phagocytes; Play; Quality of life; Radiation; Radiation induced damage; Radiation therapy; Reaction; Reagent; Recovery; Regenerative capacity; Research; Role; Salivary; Salivary Glands; Scheme; Severities; Signal Transduction; Source; Technical Expertise; Testing; Transgenic Mice; Work; Xerostomia; cell injury; cell type; cytokine; epithelial stem cell; gland development; head and neck cancer patient; improved; irradiation; monocyte; novel; novel strategies; novel therapeutics; paracrine; preservation; progenitor; restoration; saliva secretion; self-renewal; sensor; side effect; success; therapeutic target

Project Summary The long lasting decrease of saliva secretion, also called dry mouth, is common in patients treated with radiotherapy for head and neck cancer. This side effect significantly impairs the quality of life of affected patients and is difficult to remedy. The applicant’s recent work revealed that macrophages abundant in salivary glands are sharply damaged by radiotherapy, and their recovery is required for restoring saliva secretion. The goals of this proposal are to determine the roles of local macrophages in the development, maintenance and regeneration of salivary glands, and how these cells respond to radiation and restore salivary function damaged by radiation. To achieve these goals, this project will trace the origin of local macrophages under conditions mentioned above, determine effects of removing these cells on salivary function, and pinpoint which molecules are responsible for the damage of these cells by radiation and for the recovery of salivary function damaged by radiation. Completion of this project will reveal vital roles of local macrophages and their products in the maintenance of saliva secretion, and form a basis for developing novel and feasible approaches to treating dry mouth caused by radiotherapy.

项目摘要 唾液分泌的持久下降，也称为干口，在患者中很常见 用放射疗法治疗头颈癌。这种副作用严重损害 受影响的患者的生活质量很难记住。申请人最近的工作 揭示了唾液腺丰富的巨噬细胞受到的巨大破坏 放射疗法及其恢复需要恢复唾液分泌。目标的目标 建议是确定当地巨噬细胞在发展中的作用， 唾液腺的维持和再生以及这些细胞对辐射的反应 并恢复辐射损坏的唾液功能。为了实现这些目标，这个项目 将在上述条件下追踪局部巨噬细胞的起源，确定 去除这些细胞对唾液功能的影响，并查明哪些分子是 负责通过辐射和唾液的恢复来损害这些细胞 辐射损坏的功能。该项目的完成将揭示本地的重要作用 巨噬细胞及其产品维持唾液分泌，并形成基础 用于开发新颖且可行的方法来治疗由 放疗。

项目成果

Sphingosine-1-Phosphate Alleviates Irradiation Induced Salivary Gland Hypofunction through Preserving Endothelial Cells and Resident Macrophages.

• DOI: 10.3390/antiox11102050
• 发表时间: 2022-10-18
• 期刊: Antioxidants (Basel, Switzerland)