Mechanisms of inflammation-triggered taste loss and its recovery

炎症引发的味觉丧失及其恢复机制

• 批准号: 9527911
• 负责人: Hong Wang
• 金额: $ 15.4万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9527911
• 关键词: Acute; Affect; Animal Model; Autoimmune Diseases; Beverages; Biology; Body Weight decreased; Cell Death; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Chronic; Clinical; Disease; Disease model; Epithelium; Food; Functional disorder; Goals; Growth Factor; Head and Neck Cancer; Health; Homeostasis; Immune; Immune Cell Activation; Impairment; Individual; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Interferon-alpha; Investigation; Knowledge; Lead; Light; Malnutrition; Mediating; Mental Depression; Molecular; Morphology; Mouse Strains; Mus; Natural regeneration; Nerve; Nutrient; Pathology processes; Pathway interactions; Patients; Peripheral; Permeability; Pharmaceutical Preparations; Poison; Population; Process; Quality of life; Receptor Cell; Recovery; Recovery of Function; Research; Role; Stem cells; Structure; Structure of gustatory pore; Taste Bud Cell; Taste Buds; Taste Disorders; Taste Perception; Testing; Time; Tissues; Toxic effect; Transgenic Mice; Upper Respiratory Infections; Viral Cancer; Virus Diseases; base; cell type; clinically relevant; clinically significant; cytokine; cytotoxic; improved; insight; mouse model; older patient; progenitor; public health relevance; sensory system; tongue papilla; trafficking

PROJECT SUMMARY The sense of taste has evolved to detect nutrients and toxic substances in food and beverages--it is the sensory system that we rely on to make food choices. Taste dysfunction can substantially affect health: severe taste loss can lead to malnutrition, weight loss, and depression. Taste disorders can develop with various diseases, including many with underlying inflammation, such as infections and autoimmune diseases. The mechanisms of taste disorders associated with infections, autoimmune diseases, and chronic inflammatory diseases are poorly understood. Our recent research indicates that inflammation, characterized by induction of inflammatory cytokines, infiltration and activation of immune cells, may contribute to taste dysfunction. The goal of this research is to determine the molecular and cellular mechanisms of inflammation-triggered taste loss and its recovery and to explore treatment options to accelerate taste bud regeneration. The inflammatory cytokine interferon-γ (IFN-γ) is highly induced in taste epithelium in multiple disease models that show taste abnormalities. However, whether induction of IFN-γ in the taste epithelium contributes to taste loss has not been determined. To directly test the role of IFN-γ in taste loss, we have established transgenic mouse strains that allow selective induction of IFN-γ in particular cell types in the taste epithelium: taste progenitor/stem cells, sweet and umami receptor cells, and sour receptor cells. Here, we propose to use these mouse models to determine the role of IFN-γ in taste loss and to elucidate the molecular and cellular mechanisms that drive taste loss and taste bud regeneration. We will investigate the effects of IFN-γ on taste bud cell renewal, cell death, taste pore structure, taste bud permeability, and immune cell trafficking in taste papillae. In addition, we will identify the molecular and cellular processes that are critical to taste bud regeneration following taste loss triggered by inflammation. Furthermore, we will determine whether exogenous growth factors can accelerate taste bud regeneration. This research will improve our understanding of the underlying mechanisms of taste loss and taste bud regeneration and shed new light on fundamental aspects of taste biology.

项目摘要 味觉已经发展到检测食物和饮料中的营养物质和有毒物质-这是最重要的。 我们选择食物时所依赖的感官系统。味觉功能障碍会严重影响健康：严重 味觉丧失会导致营养不良、体重减轻和抑郁。味觉障碍可以发展与各种 疾病，包括许多潜在的炎症，如感染和自身免疫性疾病。的 与感染、自身免疫性疾病和慢性炎症相关的味觉障碍的机制 疾病知之甚少。我们最近的研究表明，炎症，其特征是诱导 炎性细胞因子、免疫细胞的浸润和激活可能导致味觉功能障碍。的 本研究的目的是确定炎症触发味觉的分子和细胞机制 研究味蕾的丧失及其恢复，并探索加速味蕾再生的治疗方案。炎症 在多种疾病模型中，细胞因子干扰素-γ（IFN-γ）在味觉上皮中被高度诱导， 异常然而，味觉上皮中IFN-γ的诱导是否有助于味觉丧失， 确定了为了直接测试IFN-γ在味觉丧失中的作用，我们建立了转基因小鼠品系， 允许在味觉上皮中的特定细胞类型中选择性诱导IFN-γ：味觉祖细胞/干细胞， 甜味和鲜味受体细胞以及酸味受体细胞。在这里，我们建议使用这些小鼠模型， 确定IFN-γ在味觉丧失中的作用，并阐明驱动味觉丧失的分子和细胞机制。 味觉丧失和味蕾再生。我们将研究IFN-γ对味蕾细胞更新、细胞增殖和细胞凋亡的影响。 死亡、味孔结构、味蕾渗透性和味乳头中的免疫细胞运输。另外我们 将确定分子和细胞的过程是至关重要的味蕾再生后味觉损失 是由炎症引起的此外，我们将确定是否外源性增长因素可以加速 味蕾再生这项研究将提高我们对味觉潜在机制的理解 丧失和味蕾再生，并为味觉生物学的基本方面提供了新的见解。