Atopic dermatitis (AD) is a highly pruritic, chronically relapsing, inflammatory skin disease and is characterised by acute flares and eczematous lesions with dry skin. Despite efforts by the research community to uncover its pathophysiological mechanisms, they remain elusive. Furthermore, effective guidelines of treatment are not well established with a lack of consensus about the best and safest way to apply treatments. Failure to understand the pathogenetic mechanisms and establish effective treatment guidelines will continue to affect the quality of life of existing patients and increase prevalence of the disease.

In our group, there has been a concentrated effort to study AD using a systems-biology approach, through the synthesis of mathematical modelling frameworks that integrate experimental and clinical data. Our models describe regulatory networks of key biochemical and cellular interactions related to the pathology and pathogenesis of AD. Previous models, explored the onset mechanisms of the disease, as well as, the genetic or environmental factors that trigger it, however they did not consider late stages of AD characterised by impaired adaptive immune responses.

In this thesis, we use a systems-level approach, by constructing and analysing mathematical models, to investigate AD with the aim of uncovering the mechanisms of its onset and progression, and to develop computational treatment regimens. We first develop a mathematical model of the late stages of AD, by including adaptive immune responses. The model reproduces several clinical phenotypes and suggests a qualitative pathogenic mechanism of disease progression, from early to late stages, via allergic sensitisation. By incorporating the effects of treatments in our model, we propose a theoretical framework for the computational design of patient-specific preventive and symptom management treatments. Our approach stratified patient phenotypes based on the success and effectiveness of treatment. Finally, since the process of allergic sensitisation can be mediated by a defective epidermal barrier, we propose a model of the de-novo synthesis of epidermal barrier components. With this model, we explore how the dysregulation of the networks controlling epidermal homeostasis can lead to a pathophysiologic state. This work provides a theoretical framework for the study of AD and the design of optimised patient-specific treatment protocols.