Mathematical modelling of the roles of microbiome in pathogenesis of atopic dermatitis

特应性皮炎(AD)是最常见的炎症性皮肤病。由于对该病的病理生理学缺乏了解，目前的治疗策略只是针对症状，没有根治或预防的治疗方法。鉴于这种疾病在全球范围内日益流行，以及严重阿尔茨海默病的治疗成本高昂，重要的是设计预防性治疗策略，而不是在这种慢性病患者的一生中定期应用昂贵的治疗方法。本研究的目的是了解皮肤微生物群在AD发病机制中的作用，从而制定能够预防AD的出现或治疗已患AD的症状的治疗策略。本研究的目的是了解皮肤微生物群在AD发病机制中的作用，并提出一级和二级预防策略。我们将通过开发和分析皮肤微生物群和AD病因学的系统级数学模型来解决这一问题。这一目标分为两个部分，针对一级预防(预防导致AD的过敏反应)和二级预防(预防AD早期发展以防止其变得慢性或难以控制)(图2)。术语“过敏反应”指的是训练适应性免疫反应，以对抗原作出反应，特别是产生免疫球蛋白E(IgE)抗体，从而诱发特应性疾病。在特应性疾病中，宿主适应性免疫反应向炎症反应倾斜[18]，血清IgE升高[19，20]，这是特应性疾病和严重AD的标志[21]。该项目有两个主要目标，对应于一级和二级疾病预防：目标1：确定微生物组的哪些变化可能导致过敏敏感性AD的触发。目标2：确定微生物组或免疫反应的哪些变化可能导致AD的爆发。

Atopic dermatitis (AD) is the most common inflammatory skin disease. Due to the lack ofunderstanding of the pathophysiology of the disease, current treatment strategies merely managesymptoms, and there is no curative or preventative treatment. Given the globally increasingprevalence of this disease, and high cost of therapies for severe AD, it is important to designpreventative treatment strategies, rather than applying expensive therapies regularly over the lifetimeof patients with this chronic disease. The aim of this research project is to understand the role of skinmicrobiome in AD pathogenesis and then derive treatment strategies capable of preventing theemergence of AD or treating the symptoms in those who have already developed it.The aim of this research is to understand the role of the skin microbiome in pathogenesis of AD andthen suggest primary and secondary prevention strategies. We will approach this by developing andanalysing a systems-level mathematical model of the skin microbiome and aetiology of AD. This aimis separated into two parts, directed at primary prevention (preventing allergic sensitisation whichprcedes AD), and secondary prevention (preventing AD early in development to prevent it frombecoming chronic or difficult to control) (Figure 2).The term "allergic sensitisation" refers to the training of an adaptive immune response to react to anantigen, specifically the production of immunoglobulin E (IgE) antibodies, and thereby the inductionof atopic disease. In atopic diseases, the host adaptive immune response becomes skewed towardsinflammatory responses [18], and blood serum IgE is increased [19, 20], which is a hallmark of atopicdisease, and of severe AD [21].This project has two main objectives, which correspond to primary and secondary diseaseprevention:Objective 1: To identify what changes in microbiome could be responsible for triggering allergicsensitisation AD.Objective 2: To identify what changes in microbiome or immune response could be responsible fortriggering AD flares.