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

点击翻译按钮获取中文摘要

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.