Shift to short chain fatty acids in the skin may explain AD lesions

The development of atopic dermatitis is associated with dysregulated and overactivated type two immune responses in the skin. When type two is overactivated, it blocks the healthy formation of keratinocytes skin cells and the formation of a mature skin barrier.

In this study, researchers explore the link between type two immune hyperactivation and lipid changes in skin that inhibit the skin barrier from being fully functional.

Analysis of stratum corneum lipids from the skin of patients with AD and interleukin-13-specific transgenic mice with atopic dermatitis (AD) lesions revealed a shift in epidermal lipids toward short chain fatty acids. Shorter chain fatty acids prevalent on the skin in patients with are less protective against allergens, irritants, and infections than lipids with longer carbon chains, explained the study’s co-author Donald Leung, M.D., Ph.D., of the National Jewish Health in Denver.

The findings appear in the February 22 issue of JCI Insight.

“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 Dr. Leung in a news 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.”

The investigators obtained skin samples from 30 adults with AD and 25 nonatopic controls. Lipid analysis was performed by targeted lipid chromatography. They also collected skin from lesional and nonlesional sites from IL-13 transgenic mice. In both experiments, they found a decrease in the expression of elongases three and six that take part in the process of fatty acid elongation, possibly explaining the shift from long chain fatty acids toward short chain fatty acids in all the lipid classes studied.

“Thus, here we set the foundation for an understanding of how exaggerated type 2 signaling globally affects lipid composition in the epidermis and further defines the specific link between AD lesion development and changes in epidermis lipidome,” they wrote.

REFERENCE

Evgeny Berdyshev, Elena Goleva, Irina Bronova, et al. "Lipid abnormalities in atopic skin are driven by type 2 cytokines," JCI Insight. Feb. 22, 20180.