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

特应性皮炎，通常被称为湿疹，是一种常见的皮肤疾病，影响多达五分之一的儿童和十二分之一的成年人。(1)特应性皮炎的发生被认为是环境和遗传因素共同作用的结果。然而，支撑其发展的过程仍未完全了解。T细胞通常参与防御感染，但也被认为是对特应性皮炎的重要贡献。传统上，对T细胞的研究主要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细胞的一个子集识别。（2-4）特别是，我们的研究将集中在CD1a上，它可以将这些脂质呈现给T细胞，并已被证明有助于特应性皮炎的发展。此外，许多微生物因素已被发现与特应性皮炎有关，包括真菌。然而，真菌如何促进疾病的发展和严重程度还不是很清楚。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CD1a作用的理解。然后我将研究这些T细胞是否对真菌有特异性反应。此外，我打算研究哪种真菌脂质负责触发这种皮肤炎症，以及CD1a如何在结构上与真菌脂质和T细胞相互作用。为了评估特应性皮炎患者皮肤中是否存在T细胞，我还将在个体皮肤中注射少量真菌物质后产生皮肤吸疱；这种皮肤刺激试验是常规进行过敏评估的一部分。我想进行这项研究，以提高我们对CD1a和真菌如何促进特应性皮炎发展的理解。此外，这项工作将对我们的免疫系统保护我们免受真菌侵害的方式产生见解。通过增加我们对疾病如何发生的认识，这项工作将有助于确定新的有效治疗方法。国家湿疹协会。什么是湿疹？可从：http://www.eczema.org/what-is-eczema（访问日期：2019年7月21日）Van Rhijn， I, Godfrey， D. I, Rossjohn， J. & Moody， D. B. CD1和MR1的脂质和小分子显示。2 .中华免疫学杂志，2015,643-654（2015）。CD1：抗原呈递和T细胞功能。为基础。中华免疫杂志，22,817-890(2004). 3。苏特，m.n.等。cd1限制性T细胞的鉴定和表征。免疫学杂志，1996,206.6—206.6（2016）。

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).