Ferroptosis Activation Contributes to the Formation of Skin Lesions in Psoriasis Vulgaris

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation of lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism of ferroptosis in the genesis and development of psoriasis are available. (2) Methods: Levels of lipid reactive oxygen species (ROS) and ferrous iron were measured by flow cytometry. Ultrastructure analysis was performed by transmission electron microscopy. Imiquimod-induced psoriasis-like mice were treated with a ferroptosis inducer. The expressions of mRNA of genes were measured by qRT-PCR. HaCaT cells were used to explore the function of Cyb561d2. (3) Results: In this work, we observed that levels of lipid ROS and ferrous iron in the epidermis of psoriasis vulgaris (PV) patients were increased. The existence of ferroptosis activation in the epidermis of individuals with PV was confirmed by transmission electron microscope both in patients with PV and psoriasis-like mice models. Intradermal injection of the ferroptosis inducer RSL3 in psoriasis-like mice significantly promoted and aggravated the development of psoriasis-like dermatitis, and the level of serum transferrin was also increased in PV samples. Moreover, abnormal expression of some genes related to iron metabolism was also proved in the epidermis of PV cases, among which Cyb561d2 was shown to promote ferrous iron overload and lipid peroxidation accumulation in HaCaT cells. (4) Conclusions: In summary, our study suggested that ferroptosis activation owing to iron overload may be a novel mechanism underlying the formation of skin lesions in individuals with PV.