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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.

项目摘要味觉神经和其他周围神经一样，在损伤后有再生的潜力但患者往往会留下持久的感觉缺陷。更好地理解需要再生感觉靶细胞来解决这个问题。味蕾退化当他们的相关神经受损，但重组，并成为功能，通过大部分未知的机制。在初步研究中，缺乏白细胞介素-1受体的小鼠（IL-1 R）基因在味蕾再生、神经再支配和味觉恢复方面表现出明显的延迟。神经味觉反应IL-1 R由主要的免疫调节细胞因子IL-1 R激活。 1α和IL-1β，或“IL-1”。在其他周围神经受损后，IL-1招募免疫细胞称为“白细胞”，其促进外周轴突的再生。味蕾表达IL- 1家族成员（包括IL-1 R），以及被味蕾吸引到舌头上的白细胞去神经在拟议的研究中，我们测试了味蕾中的IL-1 R信号传导的假设，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全IL-1 R敲除小鼠、用某种形式的内源性IL-1 R抑制剂治疗的小鼠，以及白细胞或味蕾中IL-1 R缺失的小鼠。我们的目标是：（1）确定角色 IL-1 R信号在味蕾再生和损伤后味觉功能恢复中的作用，其信号传导的时间要求;和（2）确定IL-1 R信号传导是否在白细胞和/或味觉受体细胞是味蕾退化、再生和神经损伤后的功能恢复。我们认为IL-1 R调节免疫反应，促进味觉祖细胞的增殖和分化之后在味蕾再生过程中。这些结果将提供洞察的基本在成年后重建味蕾的机制，以及一种新的，可能在临床上有用的损伤后感觉功能恢复的信号通路。