2026, 6(2): 117-127.
doi: 10.1515/fzm-2026-0012
Background Psoriasis is a chronic inflammatory skin disease influenced by genetic, immune, and environmental factors. Notably, its prevalence is significantly higher in colder regions, and cold climates are known to exacerbate disease symptoms. This study aimed to investigate the role of the long non-coding RNA MIR4435-2HG in regulating inflammation and cytokine production in psoriatic skin. Methods Single-cell RNA sequencing identified MIR4435-2HG expression in PDGFRB-positive mesenchymal cell subsets in psoriatic skin. Functional assays were performed to evaluate its effects on inflammatory cytokine expression in mesenchymal cells activated by TNF-α. An imiquimod-induced psoriasis mouse model was used to assess the effects of MIR4435-2HG knockdown in vivo. Results MIR4435-2HG was found to upregulate IL-6, CXCL8, and IL-17B expression in TNF-α-activated mesenchymal cells. Knockdown of MIR4435-2HG in the mouse model significantly reduced skin inflammation, epidermal hyperplasia, and psoriasis-associated cytokine expression. Conclusion MIR4435-2HG plays a critical role in regulating inflammation through mesenchymal cell activation, offering a potential therapeutic target for reducing psoriasis severity, especially in cold climates.
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