# Interaction of Ferroptosis and Immune-Mediated Inflammation in Psoriasis

## TL;DR

This paper explores how ferroptosis, a type of cell death, interacts with immune inflammation in psoriasis, suggesting it could be a new therapeutic target.

## Contribution

The paper introduces ferroptosis as a novel link between metabolic stress and immune inflammation in psoriasis.

## Key findings

- Ferroptosis-permissive niches are defined by lipid remodeling, antioxidant suppression, and iron dysregulation in psoriatic lesions.
- Modulating ferroptosis can reshape psoriasiform inflammation and amplify IL-17/TNF/IFN-γ pathways.
- Ferroptosis-related transcriptomic signatures may improve psoriasis stratification beyond cytokine profiling.

## Abstract

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation and failure of lipid repair, as a potential link between metabolic stress and immune-mediated inflammation in psoriasis. We summarize experimental evidence showing that membrane lipids remodeling, antioxidant suppression, lipid peroxidation, and dysregulated iron handling together define ferroptosis-permissive niches within psoriatic lesions. We also discuss functional studies demonstrating that ferroptosis modulation can reshape psoriasiform inflammation and explore how ferroptotic stress may amplify inflammatory signaling at the immune-epidermal interface, reinforcing IL-17/TNF/IFN-γ pathways. Finally, we discuss ferroptosis-related transcriptomic signatures as a potential approach to stratify psoriasis, capturing metabolic features that are not reflected by cytokine profiling. The translational opportunities and constraints for ferroptosis-targeted interventions are outlined, highlighting epidermal redox homeostasis as a new therapeutic frontier in psoriasis.