EZH2 may be involved in contributing to psoriasis

[Fred]

This study aimed to evaluate the expression of Enhancer of Zeste Homologue 2 (EZH2) across immune cell subsets in the peripheral blood of patients with psoriasis.

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Enhancer of Zeste Homologue 2 (EZH2) is an epigenetic regulator involved in immune cell differentiation and function; however, its role in psoriasis remains unknown.

This study aimed to evaluate EZH2 expression in peripheral blood mononuclear cells from patients with psoriasis and explore its potential functional relevance to disease pathogenesis. Peripheral blood samples were obtained from 40 psoriasis patients and 18 healthy controls, and EZH2 expression in T cell and monocyte subsets was analysed by flow cytometry. EZH2 expression was significantly reduced in circulating CD8+ naïve and memory T cells, as well as in monocyte subsets from psoriasis patients compared to healthy controls. EZH2 levels in CD8+ naïve T cells showed a significant inverse correlation with disease severity scores.

Functional analyses revealed that pharmacological EZH2 inhibition suppressed IL-17A expression in peripheral blood mononuclear cells under IL-23/IL-1β stimulation. In addition, immunofluorescence staining identified EZH2-positive T cells and monocytes within psoriatic skin lesions.

Collectively, these findings suggest that EZH2 may be involved in the regulation of type 3 inflammatory responses and may therefore represent an epigenetic regulator contributing to psoriasis pathogenesis.

Source: onlinelibrary.wiley.com

*Funding: The Japan society for the promotion of science & The Japan agency for medical research and development 

[Caroline]

Sometimes I feel that in psoriasis and psoriatic arthritis research we are zooming in so deeply on individual details that we are starting to miss the bigger picture. We see a lot of trees, but we miss to see the whole forest.

We keep identifying new molecules, pathways and cell types, IL-17 here, IL-23 there, now EZH2, and the science behind it is impressive. But psoriasis doesn’t behave like a single-pathway disease. It behaves much more like a dysregulated system, where the immune response, metabolism, stress, environment, epigenetics and long-term “inflammatory memory” all interact. By focusing on one tree at a time, we risk losing sight of the forest. Except for our own Forest Walker of course.. hope she is doing well.

That doesn’t mean this research is useless, far from it every reseach can help vision as long as you take the time to develop that overall vision. Targeted therapies have helped many people, and mechanistic insights matter. But I do wonder whether our strong detailed approach sometimes limits our understanding.
Psoriasis may not be caused by one broken switch, but by a network that has become stuck in an inflammatory mode. Until we seriously integrate systemic, lifestyle and long-term regulatory factors into research and treatment, we may keep managing symptoms very effectively while still not fully understanding the disease itself. And I think that we over here in PC already have a much wider vision than the average derm.

[Fred]

That doesn’t mean this research is useless, far from it every reseach can help vision as long as you take the time to develop that overall vision. Targeted therapies have helped many people, and mechanistic insights matter. But I do wonder whether our strong detailed approach sometimes limits our understanding.
Psoriasis may not be caused by one broken switch, but by a network that has become stuck in an inflammatory mode. Until we seriously integrate systemic, lifestyle and long-term regulatory factors into research and treatment, we may keep managing symptoms very effectively while still not fully understanding the disease itself. And I think that we over here in PC already have a much wider vision than the average derm.