Understanding the Molecular Impact of Early Intervention on Inflammatory Memory in Atopic Eczema

Why is research needed in this area? Eczema is a very common skin condition that causes redness, dryness and itch over the body. It affects physical and psychological well-being, profoundly impacting quality of life. New, potent tablet and injection treatments that affect the immune system are effective at controlling the symptoms of eczema, but are typically started too late. Once treatment is started, it is expected to be continued lifelong, carrying risks of side effects and healthcare costs. In other similar conditions caused by abnormal immune system activity such as rheumatoid arthritis and psoriasis, there is evidence that earlier treatment leads to better outcomes for patients. However, we do not fully understand the mechanisms underlying why early intervention is beneficial. Once diseases such as eczema are successfully treated, abnormal cells or molecules may remain in affected body sites such as the skin – known as an ‘inflammatory memory’. These may ‘reactivate’ in the future, causing disease to recur in the same sites. We currently do not understand much about these processes, and whether early treatment is effective because it reduces the build-up of inflammatory memory. With better understanding, we may identify new treatment strategies for eczema that target the inflammatory memory, with potential for progressing towards a cure. This knowledge may also be applicable to other inflammatory conditions. How will this research be conducted? This research is a distinct project that will use data from the ongoing mySkinomics study, which involves the collection of skin samples from patients participating in a clinical trial called BEACON (which is comparing how effective and safe various tablet and injection treatments are for adults with eczema). Skin samples are being collected before and after patients start an injection treatment called dupilumab, and examined using state-of-the-art scientific techniques. I will establish the features of inflammatory memory in eczema skin and perform experiments on cells grown in the laboratory to find out how different cells interact to form this inflammatory memory. Next, I will explore whether the duration of severe disease influences the features of inflammatory memory in eczema skin. Finally, I will investigate how these features change over time after dupilumab treatment is started, and determine whether earlier treatment is more effective at reducing or reversing the inflammatory memory in eczema skin. What does this research hope to achieve? This research aims to advance our understanding of inflammatory memory in eczema, and the effect of early treatment. This will shed light on the changes in the cells and molecules in the skin that make up inflammatory memory, and hopefully reveal why earlier treatment is more effective at correcting these abnormalities. This research will reveal valuable insights into disease processes that will be relevant to other inflammatory conditions beyond eczema, and may help us identify new treatments that target the inflammatory memory so that patients can remain disease-free and drug-free long-term. We may also gain supporting evidence to influence health policy decisions, to enable access to earlier treatment as a priority for eczema and other inflammatory conditions.