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Role of CD1a-reactive fungal lipid-specific T cells in atopic cutaneous inflammation

CD1a 反应性真菌脂质特异性 T 细胞在特应性皮肤炎症中的作用

基本信息

批准号：
MR/T028009/1
负责人：
金额：
$ 31.45万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FT028009%2F1
关键词：
Role CD1a reactive fungal lipid

项目摘要

Atopic Dermatitis, more commonly known as eczema, is a common skin condition affecting up to 1 in 5 children and 1 in 12 adults. (1) The development of atopic dermatitis is believed to result from a combination of environmental and genetic factors. However, the processes underpinning its development are still not fully understood.T cells are normally involved in defence against infection, but are also known to be crucial in contributing to atopic dermatitis. Traditionally, studies of T cells have focused on their ability to recognise proteins produced by infectious microbes. However, recent evidence indicates that microbial lipids (fats) can also be recognised by a subset of these T cells. (2-4) In particular, our investigation will focus on CD1a, which can present these lipids to T cells and which has been shown to contribute to the development of atopic dermatitis. In addition, many microbial factors have been found to be linked to atopic dermatitis including fungi. However, it is not well understood how fungi contribute to disease development and severity. Therefore, I aim to improve our understanding of the role of fungi and CD1a by collecting T cells from the blood and skin of patients diagnosed with atopic dermatitis and healthy individuals. I will then investigate if any of these T cells respond specifically to fungi. In addition, I intend to study which fungal lipids are responsible for triggering this skin inflammation, and how CD1a interacts with fungal lipids and T cells structurally. In order to assess if T cells are present in the skin of atopic dermatitis patients, I will also generate skin suction blisters after injecting small amounts of fungal material into the skin of individuals; such skin challenge testing is undertaken routinely as part of allergy assessments.I would like to conduct this research to improve our understanding of how CD1a and fungi contribute to the development of atopic dermatitis. In addition, this work will generate insights into the ways in which our immune system defends us against fungi. By increasing our knowledge of how disease occurs, the work will help identify new effective treatments.References1. National Eczema Society. What is Eczema? Available from: http://www.eczema.org/what-is-eczema (Accessed 21/07/2019)2. Van Rhijn, I., Godfrey, D. I., Rossjohn, J. & Moody, D. B. Lipid and small-molecule display by CD1 and MR1. Nat. Rev. Immunol. 15, 643-654 (2015).3. Brigl, M. & Brenner, M. B. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 22, 817-890 (2004).4. Souter, M. N. et al. Identification and characterization of CD1-restricted T cells. J. Immunol. 196, 206.6--206.6 (2016).

特应性皮炎，通常称为湿疹，是一种常见的皮肤病，影响多达1/5的儿童和1/12的成人。(1)特应性皮炎的发展被认为是由环境和遗传因素的组合引起的。然而，其发展的基础过程仍然没有完全理解。T细胞通常参与防御感染，但也被认为是导致特应性皮炎的关键。传统上，对T细胞的研究集中在它们识别感染性微生物产生的蛋白质的能力上。然而，最近的证据表明，微生物脂质（脂肪）也可以被这些T细胞的子集识别。(2-4)特别是，我们的研究将集中在CD 1a上，它可以将这些脂质呈递给T细胞，并且已被证明有助于特应性皮炎的发展。此外，已发现许多微生物因素与特应性皮炎有关，包括真菌。然而，目前还不清楚真菌如何促进疾病的发展和严重程度。因此，我的目标是通过从诊断为特应性皮炎的患者和健康个体的血液和皮肤中收集T细胞来提高我们对真菌和CD 1a作用的理解。然后我将研究这些T细胞中是否有对真菌特异性反应的。此外，我打算研究哪些真菌脂质负责触发这种皮肤炎症，以及CD 1a如何与真菌脂质和T细胞在结构上相互作用。为了评估特应性皮炎患者的皮肤中是否存在T细胞，我还将在将少量真菌材料注射到个体皮肤后产生皮肤抽吸水泡;这种皮肤激发试验是过敏评估的常规部分。我想进行这项研究，以提高我们对CD 1a和真菌如何促进特应性皮炎发展的理解。此外，这项工作将深入了解我们的免疫系统如何保护我们免受真菌侵害。通过增加我们对疾病如何发生的知识，这项工作将有助于确定新的有效治疗方法。国家娱乐协会。什么是eccampaign？可从：http://www.eczema.org/what-is-eczema（访问日期：2019年7月21日）2.货车莱茵岛戈弗雷，D.一、Rossjohn，J. & Moody，D. B。脂质和小分子通过CD 1和MR 1显示。15，643-654（2015）。Brigl，M. & Brenner，M. B。CD 1：抗原呈递和T细胞功能。Annu. Immunol.22，817-890（2004）。苏特，M. N.等，CD 1-限制性T细胞的鉴定和表征。免疫学杂志196，206.6- 206.6（2016）。