The following is a summary of “FOXE1 Contributes to the Development of Psoriasis by Regulating WNT5A,” published in the November 2023 issue of Dermatology by Liu, et al.

Psoriasis is a common, long-lasting, and recurrent inflammatory skin disease marked by an overgrowth of keratinocytes (KCs) and the invasion of immune cells. The cause of psoriasis is complicated, and only some of the exact process is known. For a study, researchers found that the forkhead box family protein FOXE1 was more abundant in psoriasis patients’ skin that had lesions compared to skin that did not have lesions. FOXE1 expression was also higher in KCs activated by M5 and a psoriasis model given imiquimod. 

They showed that FOXE1 might help KCs grow by making the G1/S transition easier and starting up the extracellular signal–regulated kinase 1/2 signaling pathway by knocking it down and overexpressing it. In addition, KCs made less IL-1β, IL-6, and TNF-α when FOXE1 was turned off. RNA-sequencing screening showed that WNT5A may be a FOXE1 downstream effector. 

Cutting down on WNT5A stopped KCs from multiplying, lowered the production of IL-1β, IL-6, and TNF-α by KCs, and lessened FOXE1’s ability to help KCs grow when overexpressed. In summary, reducing FOXE1 levels through lentiviral release of small hairpin RNAs or a genetic strategy improved dermatitis symptoms in imiquimod-induced psoriasis-like models. Altogether, their findings showed that FOXE1 plays a role in the development of psoriasis and can be used as a treatment target for psoriasis.

Source: sciencedirect.com/science/article/abs/pii/S0022202X23023990