Epidermolysis bullosa simplex (EBS) is a skin disorder caused by dominant missense mutations in KERATIN5 (KRT5) or KERATIN14 (KRT14) gene, which encode intermediate filament (IF) proteins mainly expressed in epidermal basal keratinocytes. Incorporation of mutant keratins in network of IF makes the network sensitive to stress inducing inflammation and skin blistering formation. Currently, no therapeutic approach is known. Significant cytokine imbalance in blister fluid samples from different patients was demonstrated, suggesting that EB could be considered as inflammatory disorder rather than skin disorder. The potential involvement of cytokines in EB has been little studied due to the lack of reliable in vitro model recapitulating the pathomechanisms of the human disease. We developed a pathological model of EBS using hiPSC-derived keratinocytes from patients carrying KRT5 dominant mutations (EBS-KER) compared to non-affected hiPSC-derived keratinocytes (WT-KER). Our model recapitulates phenotypes already described for EBS as keratin aggregates, demonstrating that EBS-KER represent a relevant tool for modelling EBS in vitro. To identify new molecular mechanisms, we performed RNA sequencing to compare the transcriptome of EBS-KER and WT-KER. Preliminary datas identified 139 differentially expressed genes between the 2 sub-groups. Molecular pathway and functional network analyses revealed that more 70 genes are upregulated and related to pro-inflammatory cytokine profile. These data will allow to highlight the EBS-KER's cytokines profile and to decipher their involvement in the EBS pathomechanisms. Better understanding of these cytokines in EBS could provide opportunities for new therapeutic approaches.

Towards understanding the link between cytokines profile and pathological phenotypes associated with Epidermolysis Bullosa Simplex using induced pluripotent stem cells

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.