Reduced EZH2 Expression in Circulating CD8-Positive T Cells and Monocytes in Psoriasis

Area of Science:

• Immunology
• Epigenetics
• Dermatology

Background:

• Enhancer of Zeste Homologue 2 (EZH2) is a key epigenetic regulator of gene expression.
• EZH2 influences immune cell differentiation and function, but its role in psoriasis is not well understood.

Purpose of the Study:

• To investigate EZH2 expression in immune cells of psoriasis patients.
• To explore the functional relevance of EZH2 in psoriasis pathogenesis.

Main Methods:

• Flow cytometry was used to analyze EZH2 expression in T cell and monocyte subsets from 40 psoriasis patients and 18 healthy controls.
• Peripheral blood mononuclear cells were stimulated with IL-23/IL-1β, and EZH2 inhibition was assessed.
• Immunofluorescence staining was performed on psoriatic skin lesions.

Main Results:

• EZH2 expression was significantly lower in CD8+ naïve and memory T cells and monocytes from psoriasis patients compared to controls.
• Reduced EZH2 levels in CD8+ naïve T cells inversely correlated with psoriasis disease severity.
• Pharmacological EZH2 inhibition decreased IL-17A production in response to IL-23/IL-1β stimulation.
• EZH2-positive T cells and monocytes were found in psoriatic skin lesions.

Conclusions:

• EZH2 dysregulation in immune cells may contribute to psoriasis.
• EZH2 plays a role in regulating type 3 inflammatory responses relevant to psoriasis.
• EZH2 represents a potential epigenetic target for psoriasis treatment.