Degenerative changes in the taste system

描述（由申请人提供）：周围神经损伤的影响超出了受损的神经元。然而，损伤对邻近感觉场的影响还不清楚。我们提出免疫细胞，或“白细胞”，介导味觉功能的变化。巨噬细胞对神经损伤作出反应，并延伸到舌头的未受伤区域。这些白细胞预示着正常的神经味觉反应。中性粒细胞也是对损伤的免疫反应的一部分，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中的钠转导，表明上皮钠通道（ENaC）是功能可塑性的位点。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应答者，它们诱导味觉功能缺陷;（2）神经损伤和白细胞调节ENaC表达和/或功能;（3）IL-12，一种促炎细胞因子，通过促进平衡的免疫应答在损伤后维持正常的味觉功能。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受体细胞的有益和有害影响的理解。公共卫生相关性：免疫系统在神经损伤后起着重要作用，但其对味觉系统退化的反应尚不清楚。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。更好地理解损伤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.