Atopic dermatitis (AD) may be associated with overactivity in genes involved in the production of interleukin 4 (IL-4) and interleukin 13 (IL-13), inflammatory immune molecules that may promote androgen production, drive inflammation, and fuel lipid abnormalities in skin cells of patients with the skin disorder. This is according to research findings published in Proceedings of the National Academy of Sciences.
A team of researchers stimulated human sebocytes with 10 ng/mL recombinant human cytokines that included IL-4 and IL-13. The investigators performed RNA sequencing to generate gene activity data for the model’s genome and compared these activity data with those from sebocytes not treated with the inflammatory molecules.
In their analysis, the researchers discovered that IL-4 and IL-13 stimulated expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1), a gene that generates the 3b-hydroxysteroid dehydrogenase 1 enzyme. The activity of the HSD3B1 gene significantly increased when exposed to Il-4 and IL-13.
The investigators then made the activity of HSD3B1 in sebocytes less active to assess how the gene can affect sebum output. Downregulation of the gene’s activity was associated with a decrease in sex hormones and an increase in skin sebum production. In contrast, higher HSD3B1 activity was associated with increased levels of sex hormones and less sebum production. Similar findings were reported in the investigator’s AD mouse model, as sex hormone production corresponded with a decrease in skin lipid production.
Treatment with the monoclonal antibody dupilumab was associated with significant reductions in HSD3B1 expression, further suggesting “HSD3B1 is regulated by IL-4 and IL-13 in AD skin,” the researchers wrote.
The researchers added that their “findings illuminate a connection between type 2 immunity and sex steroid hormone synthesis in the skin and suggest that abnormalities in sex steroid hormone synthesis may underlie the disrupted skin barrier in AD.”
Based on these findings, the investigators added that “targeting sex steroid hormone synthesis pathways may be a therapeutic avenue to restoring normal skin barrier function in AD patients.”
Zhang C, Chinnappan M, Prestwood CA, et al. Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis. Proc Natl Acad Sci U S A. 2021;118(38):e2100749118. doi:10.1073/pnas.2100749118