Atopic dermatitis is a common form of eczema that affects millions of people worldwide, and for which there is currently no cure. Characterised by dry skin sometimes over the entire body, and intensely itchy lesions in places such as the knees and elbows, the condition makes life extremely uncomfortable for the many people that suffer from it. Understanding how and why this form of eczema develops is critical to identifying new, more effective treatments for the disease, and new research led by Graham Ogg in the Human Immunology Unit at the WIMM holds the promise to do just that. In this latest blog post, Lauren Howson explains what they found.
The skin is actually an immune organ. It is your body’s first line of defence, as it provides a physical barrier between the outside environment and the cells that make up the tissues of your body. If the barrier is broken, it can allow irritants from the outside world to interact with your immune system. This interaction kicks your immune system into action, resulting in skin irritations such as atopic dermatitis (a type of eczema).
Atopic dermatitis is a fairly common form of eczema that affects 20-30% of the population. Although common, it is a complex disease with many factors influencing whether a person develops this skin irritation. It is already known that certain people are more susceptible to developing atopic dermatitis than others. This has been linked to mutations in genes coding for proteins that help to maintain the skin as a barrier, such as the protein filaggrin.
However, it’s not quite that simple – as people who have a mutated filaggrin protein do not always develop atopic dermatitis, so there are clearly other factors at play.
There is also evidence that the inflammation in atopic dermatitis is not a general problem associated with a dysfunctional skin barrier, but is the result of specific environmental factors that activate the immune system.
So what causes atopic dermatitis – a general barrier dysfunction which lets in environmental irritants or specific immune stimulating molecules causing inflammation? In collaboration with Vincenzo Cerundolo’s lab in the HIU, a team of scientists led by Graham Ogg have linked these two theories together in a recent publication in Science Translational Medicine.
They showed that a substance originating from the house dust mite, called phospholipase (PLA2), actually creates specific lipids (fats) in the skin which then activate a specific immune response.
Furthermore, the team found that the filaggrin protein, which maintains the skin barrier, can also act to inhibit PLA2 activityand decrease inflammation. This likely in part explains why those with filaggrin mutations are more susceptible to atopic dermatitis.
Linking barrier dysfunction (breaking the skin) with inflammation in atopic dermatitis has enhanced our understanding of this complex disease. This exciting research has also provided insight into a potential therapeutic target, PLA2, that could possibly be a target in novel treatments for atopic dermatitis in the future..
Post edited by Bryony Graham and Graham Ogg.