Degenerative changes in the taste system

描述(申请人提供)：周围神经损伤的影响超出了受损神经元的范围。然而，损伤对邻近感觉场的影响还不是很清楚。我们认为，免疫细胞，或“白细胞”，调节味觉功能的变化。巨噬细胞对神经损伤做出反应，并延伸到舌头未受损伤的区域。这些白细胞可以预测正常的神经味觉反应。中性粒细胞也是损伤免疫反应的一部分，但它们似乎对味觉功能有负面影响。神经损伤改变了味觉感受器细胞的钠转导，提示上皮钠通道(ENaC)是功能可塑性的部位。我们将检验以下假设：(1)中性粒细胞是味觉神经损伤的初始免疫反应者，并导致味觉功能障碍；(2)神经损伤和白细胞调节ENaC的表达和/或功能；(3)促炎症细胞因子IL-12通过促进平衡的免疫反应维持损伤后的正常味觉功能。这些假说的解决将增加我们对神经损伤的动态免疫反应及其对感觉感受器细胞的有益和有害影响的理解。与公共健康相关：免疫系统在神经损伤后发挥着重要作用，但它对味觉系统退化的反应还不是很清楚。拟议的研究将确定不平衡的免疫反应对味觉功能的影响，以及免疫-味觉受体细胞相互作用的机制。更好地理解对损伤的免疫反应的有益和有害影响将导致促进正常感觉功能的新策略。

Description (provided by applicant): Peripheral nerve injury has effects that extend beyond damaged neurons. However, the impact of injury on neighboring sensory fields is not well understood. We propose that immune cells, or "leukocytes", mediate changes in taste function. Macrophages respond to nerve injury, and extend to uninjured regions of the tongue. These leukocytes are predictive of normal neural taste responses. Neutrophils are also part of the immune response to injury, but they appear to have a negative effect on taste function. Neural injury alters sodium transduction in taste receptor cells, suggesting that the epithelial sodium channel (ENaC) is the site of functional plasticity. We will test the following hypotheses: (1) Neutrophils are the initial immune responders to gustatory nerve injury, and they induce deficits in taste function; (2) Nerve injury and leukocytes modulate ENaC expression and/or function; and (3) IL-12, a proinflammatory cytokine, maintains normal taste function after injury by promoting a balanced immune response. Resolution of these hypotheses will increase our understanding of dynamic immune responses to neural injury and their beneficial and harmful effects on sensory receptor cells. PUBLIC HEALTH RELEVANCE: The immune system plays an important role following neural injury, but its response to degeneration in the taste system is not well-understood. The proposed studies will determine the effects of an imbalanced immune response on taste function, and the mechanisms for immune-taste receptor cell interactions. Better understanding of the beneficial and harmful effects of the immune response to injury will lead to new strategies to promote normal sensory function.