Interleukins 4 and 13 appear to drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis, according to a new study on atopic dermatitis published in the Proceedings of the National Academy of Sciences (Sept. 21, 2021).
Investigators at the University of Texas Southwestern (UTSW) Medical Center in Dallas evaluated sebocytes, which are known to be disrupted when IL-4 and IL-13 cytokine levels are elevated, although it is not clear how these changes affect the epithelial barrier. In a bench study, the researchers found these type 2 cytokines stimulate the expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) in sebocytes. HSD3B1 is a rate-limiting gene in sex steroid hormone synthesis, and creates an enzyme called 3b-hydroxysteroid dehydrogenase 1 predominantly expressed by sebaceous glands in skin, they noted. The authors also said that HSD3B1 may cause the disruption of the skin barrier function seen in AD.
“We often think of eczema as a dry-skin condition and treat mild cases with moisturizers,” said Tamia Harris-Tryon, MD, PhD, Assistant Professor of Dermatology and Immunology at UTSW in a news release. “Here, we’re showing that a gene that’s important for making sex hormones seems to play a role in the skin making its own moisturizers. If we could alter this gene’s activity, we could potentially provide relief to eczema patients by helping the skin make more oils and lipids to moisturize itself.”
They note that a single study of dupilumab, the IL-4Ra monoclonal antibody, was shown to lower the activity of HSD3B1.
The researchers believe targeting sex steroid hormone synthesis pathways may be a way to help restore normal skin barrier function in AD patients.