Abnormalities of the permeability barrier and impaired epidermal differentiation characterize both psoriasis and atopic dermatitis, which are driven by immune responses mediated by Th1 and Th2 cytokines. The spectrum of interference of the Th1 and Th2 type cytokines with normal terminal differentiation of keratinocytes is not fully characterized. Our aim was to identify specific and common features of epidermal perturbation associated with each group of cytokines. Immortalized human keratinocytes (Ker-CT) were treated with Th1 and Th2 cytokines in pro-differentiative culture conditions with high calcium concentration. The expression of genes involved in epidermal differentiation and lipid metabolism was evaluated by RT-PCR at 2, 4 and 7 days of treatment. In parallel, Western blot analyses were performed to assess the expression levels of keratinocyte differentiation markers. Lipid composition was investigated by GCMS and LCMS at 7 days. Treatment with Th1 and Th2 cytokines showed decreased and increased expression of K10 and K6, respectively. Both Th1 and Th2 cytokines increased the expression of CCL26, CerS3, ALOX12B, FAS, FADS2 and SCD1. Conversely, LOR and CASP14, CerS6, ABCA12, ELOVL3, HMG-CoA reductase, and HMGB1 displayed low expression with both cytokine types. Specific effects of Th1 and Th2 cytokines were observed on the lipid components. Th1 cytokines inhibited significantly the calcium-induced levels of phospholipids (PCs, PEs, SMs), and free fatty acids (FFAs). Th1 and Th2 cytokines elevated and decreased, respectively, ceramides with medium to long carbon chain. Th2 cytokines promoted the accumulation of short chain ceramides and of cholesterol sulfate, as opposed to the generalized decrement of FFAs, which included long chain ones. Overall, our data indicated that the two families of cytokines feature perturbation of the lipid pathways that underlie the barrier derangement associated with psoriasis and atopic dermatitis.

ESDR217 - Distinctive and shared signatures of Th1 and Th2 cytokines on the lipid pathways involved in the epidermal barrier function

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.