Psoriasis, Cell Signaling, and Therapeutics

Psoriasis is an inflammatory skin disorder that affects 3% of the population. It is characterized by defective epidermal differentiation and results in scaly skin and skin lesions. Psoriasis development has been shown to rely on the crosstalk between immune cells, blood vessels, and keratinoctyes; however, the respective role of each of these populations in the psoriasis initiation has been a matter of debate.

In a paper published yesterday in Science Advances, researchers provide evidence that targeting signaling of VEGFA (vascular endothelial growth factor A) in the epidermis prevents psoriasis development. Despite the well-known role of VEGFA in promoting psoriasis, it has remained unclear whether VEGFA acts only on blood vessels or whether it also acts directly on the skin epidermis to orchestrate psoriasis development.

To perform the study, the team used a mouse model that overexpressed VEGFA, inducing a psoriatic-like disease. By combining VEGFA overexpression and the genetic deletion of VEGFA receptor (VEGFR1) and co-receptor (Nrp1) in the skin epidermis, the authors demonstrated that the deletion of Nrp1 or Flt1 prevents psoriasis development.

“It was very surprising to find that inhibiting VEGFA signaling only in the epidermis was sufficient to completely prevent psoriasis development including immune cell infiltration and increase in blood vessel formation mediated by VEGFA overexpression,” says first author Farida Benhadou of the Free University of Brussels.

To assess whether inhibiting Nrp1/VEGFA interaction can be of therapeutic relevance for the treatment of psoriasis, Benhadou and colleagues administrated a therapeutic anti-Nrp1 antibody that blocked the interaction between VEGFA and Nrp1 to mice with psoriasis. Administration of Nrp1 blocking antibodies induced a rapid disappearance of psoriatic lesions.

“These data demonstrate the therapeutic benefit of blocking VEGFA/Nrp1 interaction in the treatment of psoriatic disease, which may be safer for the treatment of psoriasis as compared to other therapeutic modalities that can be associated with serious side effects,” says senior author Cédric Blanpain.

Altogether, this new study demonstrates the essential role of Flt1 and Nrp1expression in the skin epidermis to mediate psoriasis development. The results of this study have important implications for the understanding of mechanisms leading to psoriasis and for treatment of the condition.