Researchers have discovered that a type-2 immune response in the skin appears to contribute to the breakdown of skin barrier function in atopic dermatitis (AD) by decreasing the proportion of long-chain fatty acids.
These findings were published online in JCI Insight (Feb. 22, 2018).
“We have long known that an activated immune system and a defective skin barrier are both important factors in eczema, but not how they are related and which one drives the disease,” said senior author Dr. Donald Y.M. Leung, in a press release. “We have now shown that the allergic immune response shortens lipids in the skin, making them less effective at maintaining moisture and more susceptible to irritants.”
Dr. Leung (pictured, left) is the division head of pediatric allergy and clinical immunology at National Jewish Health, a medical centre in Denver.
To explore the hypothesis that a hyperactivated type 2 immune response alters AD skin lipid metabolism, Dr. Leung and his colleagues first examined skin from eczema patients and healthy controls. They found lipids in the skin of eczema patients that were shorter than lipids in the skin of participants with no disease.
Photo courtesy National Jewish Health
The authors note that lipids with longer carbon chains are stronger and more water repellent than shorter chains. That means that the shorter lipids prevalent on the skin of eczema patients are not as effective at protecting the skin from trans-epidermal water loss or infiltration by pathogens or irritants.
Investigators also found that the skin of AD patients also produced fewer of the enzymes that lengthen lipid chains.
Adding the cytokines interleukin (IL)-4 and IL-13 to cultured human keratinocytes induced an elevated allergic immune response and a shortening of the skin lipids, as well as reducing the expression of lipid-lengthening enzymes.
Blocking activity of IL-4 and IL-13 in the cultured cells resulted in an abundance of long-chain lipids.
“Our findings demonstrate how the pro-allergic, type 2 immune response alters lipid formation in the skin, leading to a defective skin barrier and the dry, cracked and itchy skin in eczema,” said Dr. Leung.