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 味觉丧失会导致营养不良、体重减轻和抑郁。此外，口味的变化是一种症状， 健康状况不佳。味觉和健康之间的这种循环关系突出了研究的重要性， 了解健康和疾病中的味觉丧失。对味觉丧失的研究将为人类味觉研究提供新的途径。 疾病的预防、诊断和治疗。有充分的证据表明，感染和自身免疫性疾病 这些病症伴随着化学感觉的变化，包括味觉的变化。然而，在这方面， 目前，我们对味蕾再生是如何调节的知之甚少，也没有有效的治疗方法。 味觉丧失我们最近的研究表明，炎症，其特征在于诱导炎症反应， 细胞因子以及免疫细胞的浸润和活化，显著地促成味觉功能障碍。我们 假设炎症，特别是通过炎性细胞因子干扰素-γ（IFN-γ）作用， 通过诱导细胞死亡和抑制味蕾细胞更新而导致味觉丧失， 炎症促进味蕾再生。IFN-γ可以由各种类型的免疫和免疫调节因子产生。 非免疫细胞对感染和自身免疫的反应。它在味觉组织中的含量显著增加 在味觉丧失的自身免疫性疾病模型中。然而，IFN-γ是否直接导致味觉丧失， 确定了在这个项目中，我们建议研究炎症，特别是IFN-γ，在味觉中的作用 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。然后我们将 利用这些味觉丧失模型来研究味蕾再生的机制。这项研究将测试 关于炎症和感染如何导致味觉丧失以及味觉反应如何恢复的机制假说。 为了强调研究炎症、疾病和味觉丧失之间联系的重要性， 相当多的COVID-19患者经历味觉功能障碍。虽然大多数味觉丧失的病例 是暂时的，包括与SARS-CoV-2感染相关的味觉丧失， 一些病人。因此，这项研究的见解将有助于更好地理解一般的味觉丧失， 以及与COVID-19相关的味觉丧失。