Cytokines in the Regenerating Taste System

味觉再生系统中的细胞因子

基本信息

批准号：
10386828
负责人：
LYNNETTE Marie MCCLUSKEY
金额：
$ 32.73万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10386828
关键词：
Address Adult Affect Altered Taste Anterior Axon Biological Cell Differentiation process Cell Proliferation Cells Chronic Clinical Denervation Dental Dependence Development Ear Epithelial Exhibits Family member Fiber Functional disorder Genes Genetic Goals Head Immune Immune response Infection Injury Interleukin-1 Interleukin-1 Receptors Interleukin-1 beta Interleukins Knock-out Knockout Mice Left Leukocytes Macrophage Activation Mediating Modality Mus Natural regeneration Nerve Neurons Operative Surgical Procedures Outcome Pathway interactions Patients Peripheral Peripheral Nerves Peripheral nerve injury Population Procedures Proliferating Receptor Cell Recovery Recovery of Function Regulation Role Sensory Signal Pathway Signal Transduction Taste Buds Taste Perception Techniques Testing Time Tongue Trauma Wild Type Mouse cell regeneration cell type chorda tympani cytokine inhibitor injured insight interleukin-1 receptor type I macrophage nerve injury neutrophil novel prevent progenitor receptor recruit reinnervation relating to nervous system repaired response response to injury restoration taste system treatment strategy

项目摘要

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.

项目摘要味道神经与其他周围神经一样，受伤后有可能再生但是患者通常会持续存在持久的感觉不足。更好地理解机制需要再生感觉靶细胞来解决此问题。味蕾退化当他们相关的神经受到损害时，但已改革并通过在很大程度上未知的机制。在初步研究中，缺乏白介素-1受体的小鼠（IL-1R）基因在味蕾再生，加剧和恢复中显示出深刻的延迟神经味道反应。 IL-1R被主免疫调节细胞因子激活IL- 1α和IL-1β或“ IL-1”。损害其他周围神经后，IL-1募集免疫细胞被称为“白细胞”，可促进周围轴突的改革。味蕾表达il- 1名家庭成员（包括IL-1R），白细胞被味蕾吸引到舌头神经。在拟议的研究中，我们检验了味蕾中IL-1R信号传导的假设白细胞促进受伤后的味觉功能的恢复。我们将检验这个假设使用完整的IL-1R敲除小鼠，用内源性IL-1R抑制剂形式处理的小鼠，白细胞或味蕾中具有IL-1R缺失的小鼠。我们的目标是：（1）确定角色味蕾再生中的IL-1R信号传导以及受伤后的味觉功能的恢复，以及信号传导的临时要求；（2）确定IL-1R信号是否在白细胞和/或味觉受体细胞需要味蕾变性，再生和/或神经损伤后的功能恢复。我们建议IL-1R调节免疫反应味蕾变性，并促进味道祖细胞的增殖和分化后来在味蕾再生期间。这些结果将为基本的见解提供见识在成年期重建味蕾的机制以及一种新颖的，可能的临床用途受伤后感觉函数恢复时使用的信号通路。