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: 10359837
• 负责人: Hong Wang
• 金额: $ 35.68万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359837
• 关键词: Affect; Ageusia; Animal Model; Autoimmune Diseases; Autoimmunity; Body Weight decreased; COVID-19; COVID-19 patient; Cell Death; Cells; Diagnosis; Disease; Disease model; Epithelial; Event; Exhibits; Functional disorder; Future; Goals; Health; High Prevalence; Immune; Immune system; Infection; Infiltration; Inflammation; Inflammation Process; Inflammatory; Inflammatory Response; Injury; Interferons; Invaded; Investigation; Knowledge; Lead; Link; Malnutrition; Mediating; Mental Depression; Modeling; Molecular; Mouse Strains; Mus; Natural regeneration; Pathway interactions; Patients; Perception; Periodicity; Play; Positioning Attribute; Prevention; Process; Quality of life; Receptor Cell; Recovery; Research; Research Personnel; Resolution; Respiratory System; Role; SARS-CoV-2 infection; Signal Pathway; Signal Transduction; Signaling Molecule; Symptoms; Taste Bud Cell; Taste Buds; Taste Disorders; Taste Perception; Testing; Tissues; Toll-like receptors; Transgenic Mice; Transgenic Organisms; Viral; Viral Respiratory Tract Infection; Virus Diseases; clinically relevant; cytokine; effective therapy; experience; immune activation; influenza infection; influenzavirus; insight; novel strategies; pathogen; prevent; public health relevance; receptor; respiratory virus; response; stem cells; tissue regeneration; tissue repair; tongue papilla

PROJECT SUMMARY Taste loss can lead to malnutrition, weight loss, and depression. In addition, changes in taste are a symptom of poor health. This cyclical relationship between taste and health highlights the importance of research aimed at understanding taste loss in both health and disease. Research on taste loss will provide new approaches in the prevention, diagnosis, and treatment of disease. It is well-documented that infections and autoimmune conditions are accompanied by changes in chemosensory perception including changes in taste. However, currently we know little about how taste bud regeneration is regulated, and there is no effective treatment for taste loss. Our recent research indicates that inflammation, characterized by induction of inflammatory cytokines and infiltration and activation of immune cells, contributes significantly to taste dysfunction. We hypothesize that inflammation, particularly through the action of the inflammatory cytokine interferon-γ (IFN-γ), contributes to taste loss by inducing cell death and inhibiting taste bud cell renewal, and that resolution of inflammation promotes taste bud regeneration. IFN-γ can be produced by various types of immune and nonimmune cells in response to infections and autoimmunity. Its levels in taste tissues are markedly increased in an autoimmune disease model with taste loss. Yet, whether IFN-γ directly contributes to taste loss has not been determined. In this project, we propose to investigate the role of inflammation, especially IFN-γ, in taste loss using both a transgenic approach and a clinically relevant respiratory viral infection model. We will then use these taste loss models to study the mechanisms of taste bud regeneration. This research will test mechanistic hypotheses of how inflammation and infection cause taste loss, and how taste responses recover. To underscore the importance of research investigating the link between inflammation, disease, and taste loss, a considerable number of COVID-19 patients experience taste dysfunction. Although most cases of taste loss are temporary, including taste loss associated with SARS-CoV-2 infection, long-term taste loss can occur in some patients. Thus, insights from this research will be informative to better understand taste loss in general, as well as taste loss associated with COVID-19.

项目摘要 口味丧失会导致营养不良，体重减轻和抑郁症。此外，味道的变化是 健康状况不佳。品味与健康之间的这种周期性关系凸显了针对研究的重要性 了解健康和疾病的口味丧失。味觉丧失的研究将在 预防，诊断和治疗疾病。有充分记录的感染和自身免疫性 通过化学感知感知的变化（包括口味变化）来实现条件。然而， 目前，我们对如何调节味蕾的再生知之甚少，并且没有有效的治疗方法 口味丧失。我们最近的研究表明，炎症以诱导炎症为特征 细胞因子以及免疫细胞的浸润和激活对味道功能障碍显着贡献。我们 假设这种炎症，特别是通过炎症性细胞因子干扰素-γ（IFN-γ）的作用 通过诱导的细胞死亡和抑制味蕾的更新来促进口味丧失，并解决 炎症促进味蕾的再生。 IFN-γ可以由各种类型的免疫和 非免疫细胞响应感染和自身免疫性。它在味觉组织中的水平明显增加 在具有味觉丧失的自身免疫性疾病模型中。但是，IFN-γ是否直接导致口味丧失尚未 我们被确定了。在这个项目中，我们建议研究炎症，尤其是IFN-γ的作用 使用转基因方法和临床相关的呼吸道病毒感染模型的损失。然后我们会 使用这些味觉丧失模型研究味蕾再生的机制。这项研究将测试 注射和感染如何导致口味丧失以及口味反应如何恢复的机理假设。 为了强调研究炎症，疾病和味觉丧失之间联系的研究的重要性， 大量的COVID-19患者患有味道障碍。虽然大多数口味丧失的案例 是暂时的，包括与SARS-COV-2感染相关的味道丧失，可能会发生长期的口味丧失 一些患者。这项研究的见解将有益，以更好地了解一般的口味丧失， 以及与Covid-19相关的味觉丧失。