Immune Cell Responses in Food Hypersensitivity

食物过敏中的免疫细胞反应

• 批准号: 7640656
• 负责人: JOHN T. SCHROEDER
• 金额: $ 20.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-18 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7640656
• 关键词: Accident and Emergency department; Address; Adult; Affect; Affinity; Agonist; Allergens; Allergic; Allergic Reaction; Anaphylaxis; Antibodies; Antigen-Presenting Cells; Antigens; Basophils; Biological Assay; Biological Markers; Blood; CD4 Positive T Lymphocytes; CD80 gene; Cell Maturation; Cell physiology; Cells; Child; Childhood; Color; Data; Defect; Dendritic Cells; Disease; Effector Cell; Food; Food Hypersensitivity; Goals; Histamine; Histamine Release; Hospitals; Human; Hypersensitivity; IgE; IgE Receptors; Immune; Immune response; Immunotherapy; Inflammatory; Interleukin-12; Interleukin-3; Interleukin-4; Interleukin-6; Leukocytes; Life; Maintenance; Mediating; Mediator of activation protein; Memory; Milk; Milk Hypersensitivity; Milk Proteins; Natural Immunity; Oral; Pathogenesis; Patients; Pattern; Phase; Play; Poly I-C; Process; Production; Regulation; Respiratory System; Respiratory tract structure; Role; Serum; Stimulus; Symptoms; T-Lymphocyte; Testing; Toll-like receptors; United States; anti-IgE; cell type; cytokine; immune function; novel; oral tolerance; programs; research study; response; uptake

DESCRIPTION (provided by applicant): Food allergy affects approximately 6 to 8 percent of young children and 3 to 4 percent of adults in the United States, and is the single leading cause of life-threatening anaphylactic reactions treated in hospital emergency departments. Food hypersensitivity in general is thought to result from a defect in either the induction or maintenance of oral tolerance. The mechanisms underlying this tolerance, let alone sensitization, have yet to be elucidated. Accordingly, dendritic cells (DC) including monocytoid (mDC) and plasmacytoid (pDC) likely play a key role in this regulation. In particular, most all human DC subtypes thus far described express the high affinity IgE receptor (FceRI), indicating that these APCs function not only in sensitization but also in effector phases of allergic reactions. Our findings have prompted the general hypothesis that IgE/FceRI interactions play an important role in directing DC maturation and function by rwe have described some of these functional changes in immature DCs among adult patients with allergic respiratory tract disorders, but have yet to examine DCs from food allergic patients, including pediatric subjects. Three Aims are proposed. Aim 1 is to characterize immature DC subtypes from the blood of milk allergic subjects, milk allergic subjects who have out grown their disease, and in normal controls. Phenotypic and functional parameters will be investigated with emphasis on whether differences in adaptive vs. innate immune cytokine responses are observed among the DCs from the 3 groups of subjects. Aim 2 will simultaneously correlate DC responses with those from two effector cell types: basophils and CD4+ T-cells. The focus on basophils centers on IgE-dependent histamine release and IL-4 secretion, but also on more novel cytokines including IL-3 and IL-25. DC-dependent allergen- driven cytokines produced by CD4+ lymphocytes will be investigated using multiplexing assays with thhould add significantly to or understanding of how these cells participate in food allergy. Rare cells that are found in blood (i.e. called basophils and dendritic cells) are thought to contribute to the symptoms associated with food allergy and allergies in general. This application outlines experiments that focus on identifying differences in the responses of these white blood cells in children who are allergic to milk verses those from subjects who are no longer allergic to milk. By identifying differences (or biomarkers) that associate with these cells from milk allergic subjects, we might better understand why milk allergy persists and, more importantly, develop new strategies to treat the disease and allergies in general.

描述（由申请人提供）： 在美国，食物过敏影响大约6%至8%的幼儿和3%至4%的成年人，并且是在医院急诊室治疗的危及生命的过敏反应的单一主要原因。一般认为食物过敏是由于口服耐受性的诱导或维持缺陷所致。这种耐受性背后的机制，更不用说致敏性了，还有待阐明。因此，树突状细胞（DC），包括单核细胞样（mDC）和浆细胞样（pDC）可能在这种调节中发挥关键作用。特别地，迄今为止描述的大多数人DC亚型表达高亲和力IgE受体（FceRI），表明这些APC不仅在致敏中起作用，而且在过敏反应的效应物阶段起作用。我们的研究结果提示了一个普遍的假设，即IgE/FceRI相互作用在指导DC成熟和功能中起重要作用，我们已经描述了过敏性呼吸道疾病成人患者中未成熟DC的一些功能变化，但尚未检查来自食物过敏患者，包括儿科受试者的DC。提出了三个目标。目的1是表征来自牛奶过敏受试者、已经脱离其疾病的牛奶过敏受试者和正常对照的血液的未成熟DC亚型。将研究表型和功能参数，重点是在来自3组受试者的DC中是否观察到适应性与先天性免疫细胞因子应答的差异。目的2将同时关联DC响应与来自两种效应细胞类型的DC响应：嗜碱性粒细胞和CD4 + T细胞。对嗜碱性粒细胞的关注集中在IgE依赖性组胺释放和IL-4分泌上，但也集中在包括IL-3和IL-25在内的更多新型细胞因子上。将使用多重测定来研究由CD4+淋巴细胞产生的DC依赖性过敏原驱动的细胞因子，这将显著增加或理解这些细胞如何参与食物过敏。在血液中发现的罕见细胞（即称为嗜碱性粒细胞和树突状细胞）被认为有助于与食物过敏和一般过敏相关的症状。本申请概述了实验，重点是确定这些白色血细胞在对牛奶过敏的儿童与不再对牛奶过敏的受试者中的反应差异。通过识别与牛奶过敏受试者的这些细胞相关的差异（或生物标志物），我们可能会更好地理解为什么牛奶过敏持续存在，更重要的是，开发新的策略来治疗疾病和过敏。

项目成果

Spontaneous basophil responses in food-allergic children are transferable by plasma and are IgE-dependent.

食物过敏儿童的自发嗜碱性粒细胞反应可通过血浆转移，并且具有 IgE 依赖性。

• DOI: 10.1016/j.jaci.2013.08.033
• 发表时间: 2013
• 期刊: The Journal of allergy and clinical immunology
• 作者: Schroeder,JohnT;Bieneman,AnjaP;Chichester,KristinL;Keet,CorinneA;Hamilton,RobertG;MacGlashanJr,DonaldW;Wood,Robert;Frischmeyer-Guerrerio,PamelaA
• 通讯作者: Frischmeyer-Guerrerio,PamelaA