Cytokines in the Regenerating Taste System

项目总结 味觉神经和其他周围神经一样，在受伤后有再生的潜力。 但患者往往会留下永久性的感觉缺陷。更好地理解 为了解决这个问题，需要再生感觉靶细胞。味蕾退化 当他们的相关神经受损，但通过 很大程度上未知的机制。在初步研究中，缺乏白细胞介素1受体的小鼠 (IL-1R)基因在味蕾再生、神经再支配和味蕾恢复过程中表现出严重的延迟 神经味觉反应。IL-1R由主要的免疫调节细胞因子IL-1R激活。 1α和IL-1β，或“IL-1”。在损伤其他周围神经后，IL-1招募免疫细胞 被称为“白血球”，促进外周轴突的再生。味蕾表达IL- 1个家庭成员(包括IL-1R)，以及味蕾吸引的白细胞到舌头 神经丧失。在拟议的研究中，我们检验了IL-1R信号在味蕾中的假设 白细胞促进损伤后味觉功能的恢复。我们将检验这一假设 使用完整的IL-1R基因敲除小鼠，用某种形式的内源性IL-1R抑制物治疗的小鼠，以及 白细胞或味蕾中IL-1R缺失的小鼠。我们的目标是：(1)确定角色 IL-1R信号在味蕾再生和损伤后味觉功能恢复中的作用 其信号的时间要求；以及(2)决定IL-1R信号是否在 白细胞和/或味觉感受器细胞是味蕾退化、再生和 神经损伤后功能恢复。我们认为IL-1R调节免疫反应 味蕾变性，促进味觉祖细胞增殖分化 后来在味蕾再生期间。这些结果将为我们提供对根本问题的见解 成年期重建味蕾的机制，以及一种可能在临床上有用的新方法 信号通路在损伤后感觉功能恢复中的作用

PROJECT SUMMARY Taste nerves, like other peripheral nerves, have the potential to regenerate after injury but patients are often left with lasting sensory deficits. Better understanding of mechanisms that regenerate sensory target cells is needed to address this problem. Taste buds degenerate when their associated nerve is damaged, but are reformed and become functional through largely unknown mechanisms. In preliminary studies, mice lacking the interleukin-1 receptor (IL-1R) gene show profound delays in taste bud regeneration, reinnervation, and the recovery of neural taste responses. The IL-1R is activated by the master immune regulatory cytokines, IL- 1α and IL-1β, or "IL-1”. After damage to other peripheral nerves, IL-1 recruits immune cells known as “leukocytes” which promote the regrowth of peripheral axons. Taste buds express IL- 1 family members (including the IL-1R), as do leukocytes attracted to the tongue by taste bud denervation. In the proposed studies, we test the hypothesis that IL-1R signaling in taste buds and leukocytes promotes the recovery of taste function after injury. We will test this hypothesis using full IL-1R knockout mice, mice treated with a form of the endogenous IL-1R inhibitor, and mice with IL-1R deletion in leukocytes or in taste buds. Our aims are to: (1) Determine the role of IL-1R signaling in taste bud regeneration and the recovery of taste function after injury, and the temporal requirements for its signaling; and (2) Determine whether IL-1R signaling in leukocytes and/or taste receptor cells is required for taste bud degeneration, regeneration, and functional recovery after nerve injury. We propose that IL-1R regulates immune responses to taste bud degeneration, and promotes the proliferation and differentiation of taste progenitors later during taste bud regeneration. These results will provide insight to fundamental mechanisms that rebuild taste buds in adulthood, and a novel, possibly clinically-useful signaling pathway used in the recovery of sensory function after injury.