Mechanisms of peanut (A. hypogaea) glycan adjuvanticity.

花生（A.hypogaea）聚糖佐剂的机制。

基本信息

批准号：
8013725
负责人：
WAYNE G SHREFFLER
金额：
$ 8.23万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8013725
关键词：
Accounting Address Adjuvant Adjuvanticity Affect Allergens Allergic Allergy to peanuts American Anaphylaxis Antibodies Antigens Arachis hypogaea Arthropods Aspergillus Attention Bacteria Bacterial Proteins Bee Venoms Betula Genus Binding Bone Marrow C-Type Lectins CD80 gene Carbohydrates Caseins Cell Line Cells Clinical Complement Complex Crustacea Cytoplasmic Tail Data Dendritic Cells Dendritic cell activation Dictyoptera Diet Endocytosis Inhibition Epithelial Cells FOS gene Family member Feces Future Gene Activation Genes Genetic Polymorphism Genetic Transcription Glycoproteins Helminths Human Hypersensitivity Immune Immune response Immune system Immunity Immunoblotting Immunologic Receptors Immunoprecipitation In Vitro Individual Inflammation Insecta Interleukin-12 Interleukin-15 Interleukin-6 Kinetics Lead Lectin Ligands Ligation Link Lipids Lipopolysaccharides Mammals Mannose Measurement Measures Mediating Mediator of activation protein Mentors Methods Mitogen-Activated Protein Kinases Molecular Mouse Strains Mus Mutation Nut Hypersensitivity Orthologous Gene Ovum Parasitic infection Pathway interactions Pattern Peanuts - dietary Peptides Phenotype Phospholipase A2 Phosphorylation Plants Play Pollen Polysaccharides Prevalence Principal Investigator Property Protein Tyrosine Kinase Proteins Public Health Publishing RNA Reporting Research Research Personnel Research Proposals Reverse Transcriptase Polymerase Chain Reaction Role Schistosoma Schistosoma mansoni Sentinel Signal Pathway Signal Transduction Small Interfering RNA Solubility Source Structure Surface T-Cell Proliferation T-Lymphocyte TCR Activation TLR2 gene TNFRSF5 gene TNFSF4 gene TSLP gene Testing Th1/Th2 Differentiation Pathway Therapeutic Time Transgenic Mice Tyrosine Ursidae Family Virus Zymosan base cytokine dectin 1 egg in vivo knock-down macromolecule mouse model notch protein novel pathogen programs receptor research study response sugar transcription factor uptake

项目摘要

DESCRIPTION (provided by applicant): This research proposal is based on the clinical observation that a small number of potential allergens that humans encounter account for the large majority of allergic responses. The immune system's sentinel cells, dendritic cells (DC), play a crucial role instructing and boosting the specific and long-lasting immune response to antigen. Many pathogen-associated molecules are known to promote effective immunity to bacteria and viruses (Th1 immunity). However, few signals that promote allergic-type (Th2 immunity) immune responses have been characterized in molecular detail. An exception to this is certain related sugar structures identified from parasitic worms, which have been shown to be both necessary and sufficient as Th2 immune boosters. Sugar structures of this type are common in plants, arthropods (e.g., crustaceans, insects), and parasitic worms - but not mammals. This suggests that recognition of these sugar structures may have evolved to protect humans against parasitic infections. Recognition of such structures associated with potential allergens, may contribute to the establishment of an allergic response in some individuals. Our preliminary data suggest that sugar structures from peanut are necessary for uptake and activation of DC through specific receptors to induce strong Th2 immunity. We will further test this hypothesis and identify active molecules from peanut by testing fractions of soluble peanut extract for the capacity to activate DC (Aim I). We will identify the receptor(s) and mechanisms involved in DC activation by peanut sugars (Aim II). We will also test the importance of these sugars for the induction of peanut anaphylaxis using a mouse model of peanut allergy established by my mentor (Aim III). Relevance: Allergy to peanut (Arachis hypogaea) tends to be persistent and severe. More than 3 million Americans have peanut and/or tree nut allergy. This project attempts to contribute to our understanding of why peanut allergy is particularly common and persistent. Better understanding of the mechanisms that contribute to the establishment of allergic responses may eventually be used in novel preventative or therapeutic strategies.

描述（由申请人提供）：该研究建议基于以下临床观察，即人类遇到的少数潜在过敏原是大多数过敏反应。免疫系统的前哨细胞树突状细胞（DC）在指导和增强对抗原的特定和持久的免疫反应方面起着至关重要的作用。已知许多与病原体相关的分子促进对细菌和病毒的有效免疫（TH1免疫）。但是，很少有促进过敏反应（Th2免疫）免疫反应的信号已通过分子细节进行表征。一个例外是从寄生虫蠕虫中确定的某些相关糖结构，这些糖结构已被证明是Th2免疫助推器的必要且足够的。这种类型的糖结构在植物，节肢动物（例如，甲壳类动物，昆虫）和寄生虫蠕虫中很常见 - 但却不是哺乳动物。这表明对这些糖结构的识别可能已经进化，以保护人类免受寄生虫感染。认识到与潜在过敏原相关的这种结构，可能有助于某些个体建立过敏反应。我们的初步数据表明，来自花生的糖结构对于通过特定受体摄取和激活DC是必需的，以诱导强大的Th2免疫力。我们将进一步检验该假设，并通过测试可溶性花生提取物的分数来激活DC（目标I），从而鉴定出花生的活性分子。我们将确定花生糖激活DC激活的受体和机制（AIM II）。我们还将使用我的导师（AIM III）建立的花生过敏的小鼠模型来测试这些糖对诱导花生过敏反应的重要性。相关性：对花生过敏（Arachis hypogaea）往往是持久而严重的。超过300万美国人患有花生和/或树坚果过敏。该项目试图有助于我们对为什么花生过敏特别普遍且持久的理解。更好地理解有助于建立过敏反应的机制，最终可以用于新颖的预防或治疗策略中。