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Understand mechanisms of mast cell reactivity and induced anergy and how these are modulated by biologics in food allergy treatment

了解肥大细胞反应性和诱导无反应性的机制，以及在食物过敏治疗中生物制剂如何调节这些机制

基本信息

批准号：
2456902
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2456902
关键词：
Understand mechanisms mast cell reactivity

项目摘要

Allergic diseases, such as asthma, allergic rhinitis, and food allergy, are an important public health burden and seriously affect the quality of life of people, particularly in developed countries. These conditions are characterized by the presence of IgE antibodies to common things in our environment, such as house dust mite (asthma), pollen (allergic rhinitis), and peanut (food allergy). The routes of allergens intake and the frequency are highly variable. For example grass pollen exposure is seasonal while food allergens are taken up accidentally and through the gastrointestinal tract. The symptoms associated with the latter are more systemic and severe compare to the inhalant allergen. Mast cells, together with basophils, are the main effector cells in IgE-mediated allergic reactions. During the allergic response, mast cells upon allergen encounter are activated and subsequently release rapidly their granular content, including histamine, cytokines, chemokines, proteases, and lipid mediators.Furthermore, the cytokine IL-33, produced by damaged epithelial cells contributes to acute allergic reactions by enhancing the IgE-mediated activation of mast cells. For patients allergic to multiple allergens, knowing which allergen or combinations of allergens are driving the symptoms is clinically relevant and as of yet is a poorly understood area. Furthermore, it remains unclear how allergen re-exposure, as well as combinations of unrelated allergens, affect mast cell activities. In addition, it is unclear what is the effect of treatment with biologics on mast cell responsiveness Therefore, the goal of the project is to gain a better understanding of the role of human mast cells in complex multi-allergen dominated allergic responses and investigate mechanisms of mast cell unresponsiveness. This project involves culturing and differentiation of human mast cells and the evaluation of their function by flow cytometry (e.g. CyTOF), advanced immunofluorescence, transcriptomic analysis and bioinformatics analysis. Moreover, this project will be combining mast cell-centred immunology research and allergy clinical expertise at the internationally recognised Manchester Collaborative Centre of Inflammation Research and Lydia Becker Institute of Immunology and Inflammation.

过敏性疾病，如哮喘、过敏性鼻炎和食物过敏，是一个重要的公共卫生负担，严重影响人们的生活质量，特别是在发达国家。这些条件的特点是存在IgE抗体的共同的东西在我们的环境中，如屋尘螨（哮喘），花粉（过敏性鼻炎），和花生（食物过敏）。过敏原的摄入途径和频率是高度可变的。例如，草花粉暴露是季节性的，而食物过敏原是通过胃肠道意外摄入的。与吸入性过敏原相比，与后者相关的症状更全身性和严重。肥大细胞与嗜碱性粒细胞一起是IgE介导的过敏反应中的主要效应细胞。在过敏反应过程中，肥大细胞在接触过敏原时被激活，随后迅速释放其颗粒状内容物，包括组胺、细胞因子、趋化因子、蛋白酶和脂质介质。此外，由受损上皮细胞产生的细胞因子IL-33通过增强IgE介导的肥大细胞激活而促进急性过敏反应。对于对多种过敏原过敏的患者，了解哪种过敏原或过敏原的组合正在驱动症状是临床相关的，并且到目前为止是一个知之甚少的领域。此外，过敏原再暴露以及不相关过敏原的组合如何影响肥大细胞活性仍不清楚。此外，目前还不清楚生物制剂治疗对肥大细胞反应性的影响，因此，该项目的目标是更好地了解人类肥大细胞在复杂的多变应原主导的过敏反应中的作用，并研究肥大细胞无反应性的机制。该项目涉及人肥大细胞的培养和分化，并通过流式细胞术（如CyTOF），先进的免疫荧光，转录组学分析和生物信息学分析来评估其功能。此外，该项目将结合以肥大细胞为中心的免疫学研究和国际公认的曼彻斯特炎症研究合作中心和Lydia Becker免疫学和炎症研究所的过敏临床专业知识。