Mechanisms of inflammation-triggered taste loss and its recovery

项目总结 味觉已经进化到可以检测食物和饮料中的营养物质和有毒物质--它是 我们赖以做出食物选择的感官系统。味觉障碍会严重影响健康：严重 味觉缺失会导致营养不良、体重减轻和抑郁。味觉障碍可发展为不同的 疾病，包括许多潜在的炎症，如感染和自身免疫性疾病。这个 与感染、自身免疫性疾病和慢性炎症性疾病相关的味觉障碍的机制 人们对疾病知之甚少。我们最近的研究表明，炎症的特征是诱导 炎性细胞因子，免疫细胞的渗透和激活，可能导致味觉功能障碍。这个 这项研究的目的是确定炎症触发的味觉的分子和细胞机制 并探索加速味蕾再生的治疗方案。炎症性的 细胞因子干扰素-γ(干扰素-γ)在多种味觉疾病模型中高度诱导味觉上皮细胞表达 异常现象。然而，在味觉上皮细胞中诱导干扰素-γ是否会导致味觉丧失还没有 已经确定了。为了直接测试干扰素-γ在味觉丧失中的作用，我们建立了转基因小鼠品系。 允许选择性地诱导味觉上皮中特定细胞类型的干扰素-γ：味觉祖细胞/干细胞， 甜味和鲜味感受器细胞以及酸味感受器细胞。在这里，我们建议使用这些小鼠模型来 确定干扰素-γ在味觉丧失中的作用，并阐明其分子和细胞机制 味觉丧失和味蕾再生。我们将研究干扰素-γ对味蕾细胞更新、细胞 死亡，味孔结构，味蕾通透性，以及免疫细胞在味觉乳头中的运输。此外，我们 将确定味觉丧失后味蕾再生的关键分子和细胞过程 是由炎症引发的。此外，我们还将确定外生增长因素是否可以加速 味蕾再生。这项研究将提高我们对味觉潜在机制的理解 失去和味蕾再生，并为味觉生物学的基本方面提供了新的线索。

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.