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HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY

过敏中不依赖组胺的肥大细胞神经相互作用

基本信息

批准号：
9908041
负责人：
Qin Liu
金额：
$ 38.13万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-12 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908041
关键词：
Adrenal Cortex Hormones Affect Afferent Neurons Allergic Allergic Conjunctivitis Allergic Disease Antihistamines Axon Behavioral Calcium Cell Degranulation Chronic Clinical Clinical Treatment Communication Cyclosporine Data Development Drug Targeting Eczema Family Fiber G-Protein-Coupled Receptors Generations Genes Genetic Histamine Human Hypersensitivity Imaging Techniques Knowledge Ligands Mediating Molecular Molecular Genetics Mucous Membrane Mus Neuraxis Neurodermatitis Neurons Opioid Pathogenesis Pathway interactions Peptides Peripheral Pharmaceutical Preparations Pharmacology Physiological Play Prevention Productivity Pruritus Quality of life Refractory Role Sensory Signal Transduction Skin Specificity Spinal Cord Spinal Ganglia Structure of trigeminal ganglion Symptoms Testing Therapeutic Tissue membrane Transgenic Mice Translating Urticaria base behavioral response behavioral study experimental study genetic approach human subject imaging approach in vivo in vivo evaluation innovation mast cell neuropeptide FF novel novel therapeutic intervention pain signal prevent receptor reconstitution relating to nervous system side effect

项目摘要

Itch is a primary symptom of many allergic conditions, and severely affects the quality of life and productivity. Primary sensory neurons residing in the trigeminal ganglia and dorsal root ganglia (DRG) play an essential role in the generation of allergic itch. These neurons detect endogenous itch-inducing molecules (pruritogens) via a group of itch receptors on their peripheral axons in the skin or mucosal membrane tissues, and transmit signals to the spinal cord via their central axons. In contrast to the well-studied histamine pathway, histamine-independent itch pathways in allergic itch remain poorly defined. Previously, we identified several novel itch receptors within a large family of G-protein‒coupled receptors called Mrgprs. We found that several Mrgprs recognize distinct pruritogens, and mediate histamine-independent itch. Our latest results indicate that Mrgprs are required for mast cell-mediated allergic itch. This proposal aims to uncover the underlying mechanisms. We will test whether Mrgprs mediate the interaction between mast cells and primary sensory fibers in allergic itch using molecular, genetic and imaging approaches in Aim 1. Furthermore, we will identify the endogenous Mrgpr ligands released by mast cells upon degranulation in Aim 2. In Aim 3, we seek to translate our discoveries from mice to humans. Human Mrgprs do not form clear orthologous pairs with mouse Mrgprs. Their role in itch is therefore unclear. Based on our preliminary data, we hypothesize that human MrgprX1 mediates neuronal and behavioral response to mast cell-mediated allergy, which will be tested in Aim 3. These studies will reveal the neural basis underlying allergic itch and will have a significant impact on both the study of itch pathogenesis and the clinical treatment of itch.

瘙痒是许多过敏性疾病的主要症状，严重影响生活质量和健康