Eukaryotic translation initiation factor 4E (eIF4E) has been known to play a critical role in the regulation of gene expression in eukaryotes and to affect many essential cellular processes, including proliferation, apoptosis and differentiation. We and others found eIF4E and other eIF subunits upregulated in human psoriatic skin and thus hypothesized that they are involved in the pathophysiology of psoriasis and can serve as direct topical targets for anti-psoriatic treatment. We used specific eIF4E siRNA or briciclib an eIF4E inhibitor in HaCaT cells, a human 3D-psoriasis tissue model as well as the imiquimod and TGFß mouse model to downregulate the protein and mRNA expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (e.g. eIF1A, eIF2α, eIF3A, eIF3B, eIF5 and eIF6). This inhibition abolished psoriatic inflammation in both the imiquimod and TGFß mouse model, as well as in a human 3D-psoriasis tissue model. Downregulation of eIF4E and the other eIFs by application of briciclib (particularly when given topically) was linked to the normalization of cellular proliferation, restoration of the inflammatory milieu and epidermal hyperplasia of psoriasis, and normalization of levels of pro-inflammatory cytokines (e.g. TNFα, IL-1b, IL-17 and IL-22), as well as keratinocyte differentiation markers (e.g. KRT16 and FLG). These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up new avenues for the development of novel topical anti-psoriatic treatment strategies by targeting eIF4E and/or other eIFs.

ESDR374 - Eukaryotic translation initiation factor 4E (eIF4E) as a target of anti-psoriatic treatment

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.