Extracellular Vesicles from miR-146a Overexpressing Mesenchymal Stem Cells Attenuate ‎Imiquimod-Induced Psoriasis by Regulating Cytokine Expression

Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. To investigated the effectiveness of extracellular ve...

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Published in:Iranian journal of immunology Vol. 22; no. 2; p. 119
Main Authors: Shao, Hongmei, Chen, Junjie
Format: Journal Article
Language:English
Published: Iran Shiraz Institute for Cancer Research 23.06.2025
Subjects:
Cytokines
Erythema
Extracellular vesicles
IL-1β
Imiquimod
Interleukin 10
Interleukin 17
Interleukin 23
Interleukin 4
Interleukin 6
Intravenous administration
Lysates
Mesenchymal stem cells
miRNA
Psoriasis
Skin diseases
Skin lesions
Stem cells
Transforming growth factor-b
Tumor necrosis factor-α
γ-Interferon
Mesenchymal stem cell
Psoriasis
Extracellular vesicle
Exosome
Cytokine
ISSN:1735-1383, 1735-367X, 1735-367X
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Summary:Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. To investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis. To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-γ, IL-17, TNF-α, IL-23, IL-6, IL-1β, TGF-β, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques. The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-γ, IL-17, TNF-α, IL-23, IL-6, and IL-1β were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-β, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice. EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.
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ISSN:1735-1383
1735-367X
1735-367X
DOI:10.22034/iji.2025.104576.2909