Mechanisms of inflammation-triggered taste loss and its recovery

炎症引发的味觉丧失及其恢复机制

基本信息

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
项目类别：
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

项目摘要

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.

项目概要味觉已经进化到可以检测食物和饮料中的营养成分和有毒物质——它是我们用来选择食物的感觉系统功能障碍会严重影响健康：严重。味觉丧失会导致营养不良、体重减轻和各种抑郁症。疾病，包括许多具有潜在炎症的疾病，例如感染和自身免疫性疾病。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我们最近的研究表明，炎症的特点是诱发。炎症细胞因子、免疫细胞的浸润和激活可能导致味觉功能障碍。这项研究的目标是确定炎症引发味觉的分子和细胞机制损失及其恢复，并探索加速味蕾再生的治疗方案。在多种显示味觉的疾病模型中，细胞因子干扰素-γ (IFN-γ) 在味觉上皮细胞中被高度诱导然而，味觉上皮细胞中 IFN-γ 的诱导是否会导致味觉丧失尚无定论。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。允许在味觉上皮细胞中的特定细胞类型中选择性诱导 IFN-γ：味觉祖细胞/干细胞，在这里，我们建议使用这些小鼠模型来检测甜味和鲜味受体细胞。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我们将研究 IFN-γ 对味蕾细胞更新、细胞的影响。死亡、味孔结构、味蕾通透性和味乳头中的免疫细胞运输。将识别对味觉丧失后味蕾再生至关重要的分子和细胞过程此外，我们将确定外源性生长因子是否可以加速。这项研究将提高我们对味觉潜在机制的理解。损失和味蕾再生，并为味觉生物学的基本方面提供了新的线索。