|Why babies develop eczema is not yet well understood. Professor Ben|
Marsland is senior author on a new paper on the skin's microbiome.
The group continued on with their more fundamental research on atopic dermatitis to try and understand the rules which govern the skin and determine whether they could identify factors that might be the focus of future intervention studies.
In their recent paper, they show in a mouse model that the microbiome - the family of all the microbes that live on and inside the human body - is a key determinant of the immunological landscape of the skin.
As the microbiome develops on the skin, it ‘educates’ cells and leads to the production of chemokines, which are local messenger molecules, that recruit antigen presenting cells (APCs), i.e. cells that flag pathogens to the immune system, which then develops a response. These APCs are required to initiate and drive inflammation in the skin. This inflammation is important for protection against pathogens, but unfortunately, it is also capable of initiating allergic responses. Thus, normal formation of the skin microbiome is a double-edged sword — on the one hand it makes sure the immune system is capable of fighting pathogens, but on the other, the response to allergens can be an overreaction, and thus cause allergies.
Professor Ben Marsland said that a further intriguing finding in this study, although it needs further investigation, was that "a diverse skin microbiome is associated with better integrity of the skin barrier. In fact, even a diverse skin microbiome shortly after birth resulted in a level of skin integrity similar to that of a healthy adult animal.
"These data raise the idea that perhaps a ’skin microbial transfer’ could be applied to newborns to improve their skin barrier function, potentially protecting them against allergens in the environment from penetrating the skin leading to systemic sensitisation, which might underlie other types of allergic diseases such as food allergy and asthma. Further preclinical studies are needed to see whether this intervention might be efficacious," he said.
Finally, Staphylococcus aureus (popularly known as 'golden staph') is a bacteria that is often linked with atopic dermatitis and plays a pathogenic role in the disease. Professor Marsland said, "We wondered what came first? Did the Staphylococcus initiate inflammation or did inflammation initiate a flare-up of Staphylococcus? Our data suggest that in fact inflammation comes first. Staphylococcus is a normal microbial resident on the skin.
"However, in order for the Staphylococcus to expand and cause further inflammation, the immune system had to create an environment that suited this bacteria; which turns out to be inflammation and damaged skin. Thus, at least in this preclinical model, we have made progress towards understanding the mechanisms through which Staphylococcus might drive disease, and identified the skin microbiome-immune cell cross talk as an upstream regulator that might offer the best opportunities for further intervention strategies."
Ubags ND, Trompette A, Pernot J, ..., Nicod LP, Harris NL, Marsland BJ. Microbiome-induced antigen presenting cell recruitment coordinates skin and lung allergic inflammation. Journal of Allergy and Clinical Immunology (JACI). https://doi.org/10.1016/j/jaci.2020.06.030