Work

Topical cyanidin attenuates IL-17 A-driven keratinocyte ferroptosis and cutaneous inflammation in psoriasis

Year: 2026

Type: article

Abstract: Exacerbation of iron-catalyzed lipid peroxidation and consequent dendritic cell activation are common denominators of keratinocyte ferroptosis, thereby sustaining a pathological loop in psoriasis. However, the molecular mechanism underlying immunogenic ferroptosis and its therapeutic implications in psoriasis remain to be elucidated. Herein, we identified a new perspective on IL-17 A, which is clinically significant in psoriasis, as orchestrating keratinocyte ferroptosis through a previously unknown mechanism. Pharmacological ablation of IL-17 A signaling via topical application of cyanidin (an anthocyanin-based compound previously shown to inhibit the IL-17 A/IL-17RA interaction) inhibits iron-catalyzed lipid peroxidation, thereby mitigating disease in an experimental model of psoriasis. Our investigations with HaCaT keratinocytes cultured in a psoriatic-like microenvironment also revealed compelling evidence that suppression of IL-17RA or cyanidin treatment desensitizes the transferrin receptor (TfR) and improves Pcbp1 activity, thereby impacting iron metabolism towards ferroptosis. The elevated Pcbp1 levels were concomitantly associated with reduced EMT transcription factor, Zeb1, which fails to engage Gpx4 transcriptional machinery that contributes to ferroptosis activity in these keratinocytes. Importantly, application of cyanidin cream successfully attenuates the secondary immune response, triggered by overactivation of dendritic cells, a pathological consequence of ferroptosis. Conclusively, our work highlights the potential significance of IL-17 A as a targeted therapeutic target for repurposing cyanidin in a new topical approach to manage psoriasis.

Source: Scientific Reports

DOI: 10.1038/s41598-026-66740-6

Authors: Arulkumaran Rithvik, Snigdha Samarpita, Mahaboobkhan Rasool

Institution: Vellore Institute of Technology University

Language: English

Topic: Psoriasis: Treatment and Pathogenesis

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690