Background: eIFs play a critical role in the regulation of gene expression in eukaryotes ans affect many essential cellular processes, including proliferation, apoptosis and differentiation. Purpose of the study: We hypothesized that eIFs are involved in the pathophysiology of psoriasis, are affected by anti-psoriatic treatments, and can serve as direct targets for anti-psoriatic treatment. Experimenetal design:We used the IMQ and TGFß transgenic mouse models, human psoriasis samples (lesional psoriatic and healthy control skin) as well as an 3D in vitro model of psoriasis to enable the study of the disease, and to screen therapeutic candidates ( eIF1A and eIF3B) to assess the therapeutic potential and to determine the molecular mechanisms related to anti-psoriatic response with regard to the translation initiation machinery.Results: Our preliminary data showed significant increase of eIF1A and eIF3B in human psoriasis lesions, IMQ and TGFß mice, as well as in HaCaT cells on protein and mRNA level. Our preliminary 3D in vitro model and mouse model (IMQ and TGFß) data revealed that a systemically and topically treatment with eIF1A and eIF3B siRNA decrease epidermis and dermis thickness as well as reduced mRNA expression for eIF1A and eIF3B after treatment. Conclusion: We have demonstrated for the first time an increased expression of eIF1A and and eIF3B in psoriatic skin. This project will extend the knowledge of the mechanisms behind the translation initiation in particular of eIFs in psoriasis, but may also reveal novel cellular processes regulated by eIFs. Together, this may open up new therapeutic avenues by targeting eIFs in psoriasis.

ESDR169 - Eukaryotic Translation Initiation Factors (eIFs): Potential Therapeutic Targets in Psoriasis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING