iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory disease characterized by severe itching and eczematous lesions. Despite various treatments, AD patients experience side effects and fail to achieve full remission. This study investigated the therapeutic potential of extracellular vesicles (E...

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Main Authors: Soo Kim, Jimin Kim, Ran Kim, Hongduk Kim, Seul Ki Lee, Seon‐Yeong Jeong, Haedeun You, Somi Park, Tae Min Kim
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Journal of Extracellular Biology
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Online Access:https://doi.org/10.1002/jex2.70067
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author Soo Kim
Jimin Kim
Ran Kim
Hongduk Kim
Seul Ki Lee
Seon‐Yeong Jeong
Haedeun You
Somi Park
Tae Min Kim
author_facet Soo Kim
Jimin Kim
Ran Kim
Hongduk Kim
Seul Ki Lee
Seon‐Yeong Jeong
Haedeun You
Somi Park
Tae Min Kim
author_sort Soo Kim
collection DOAJ
description ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory disease characterized by severe itching and eczematous lesions. Despite various treatments, AD patients experience side effects and fail to achieve full remission. This study investigated the therapeutic potential of extracellular vesicles (EVs) derived from IFN‐γ‐primed induced mesenchymal stem cells (IFN‐γ‐iMSC‐EVs) in a 2,4‐dinitrochlorobenzene (DNCB)‐induced AD mouse model. We also examined whether IFN‐γ‐iMSC‐EVs could suppress IL‐4/13‐induced Th2 responses in keratinocytes. The therapeutic outcome of IFN‐γ‐iMSC‐EVs was comparable to or more effective than baricitinib or clobetasol. While severe weight loss was observed in mice treated with clobetasol, no significant weight reduction occurred in those receiving IFN‐γ‐iMSC‐EVs. Histological analysis demonstrated reduced skin thickness, decreased infiltration of mast cells and inflammatory cells, and suppression of the Th2 immune response, as evidenced by decreased signalling of IL‐4, IL‐13, and IL‐31. IFN‐γ‐iMSC‐EVs also led to a greater reduction in inflammation and pruritus compared to baricitinib and clobetasol. Additionally, skin barrier integrity and epidermal protein expression were improved in IFN‐γ‐iMSC‐EVs. In IL‐4/13‐stimulated keratinocytes, the decrease in JAK1/2 gene expression and the increase in Keratin 1 gene expression were more prominent in IFN‐γ‐iMSC‐EVs than in baricitinib. The results suggest that IFN‐γ‐iMSC‐EVs have the potential to inhibit AD progression and represent a novel therapeutic option for AD.
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publishDate 2025-06-01
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spelling doaj-art-2155cec7b7634787b0b78c87e65e65c62025-08-20T02:22:09ZengWileyJournal of Extracellular Biology2768-28112025-06-0146n/an/a10.1002/jex2.70067iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune ResponsesSoo Kim0Jimin Kim1Ran Kim2Hongduk Kim3Seul Ki Lee4Seon‐Yeong Jeong5Haedeun You6Somi Park7Tae Min Kim8Brexogen Research Center Brexogen Inc. Seoul South KoreaBrexogen Research Center Brexogen Inc. Seoul South KoreaGraduate School of International Agricultural Technology Seoul National University Pyeongchang Gangwon‐do South KoreaInstitutes of Green‐Bio Science and Technology Seoul National University Pyeongchang Gangwon‐do South KoreaBrexogen Research Center Brexogen Inc. Seoul South KoreaBrexogen Research Center Brexogen Inc. Seoul South KoreaBrexogen Research Center Brexogen Inc. Seoul South KoreaBrexogen Research Center Brexogen Inc. Seoul South KoreaGraduate School of International Agricultural Technology Seoul National University Pyeongchang Gangwon‐do South KoreaABSTRACT Atopic dermatitis (AD) is a chronic inflammatory disease characterized by severe itching and eczematous lesions. Despite various treatments, AD patients experience side effects and fail to achieve full remission. This study investigated the therapeutic potential of extracellular vesicles (EVs) derived from IFN‐γ‐primed induced mesenchymal stem cells (IFN‐γ‐iMSC‐EVs) in a 2,4‐dinitrochlorobenzene (DNCB)‐induced AD mouse model. We also examined whether IFN‐γ‐iMSC‐EVs could suppress IL‐4/13‐induced Th2 responses in keratinocytes. The therapeutic outcome of IFN‐γ‐iMSC‐EVs was comparable to or more effective than baricitinib or clobetasol. While severe weight loss was observed in mice treated with clobetasol, no significant weight reduction occurred in those receiving IFN‐γ‐iMSC‐EVs. Histological analysis demonstrated reduced skin thickness, decreased infiltration of mast cells and inflammatory cells, and suppression of the Th2 immune response, as evidenced by decreased signalling of IL‐4, IL‐13, and IL‐31. IFN‐γ‐iMSC‐EVs also led to a greater reduction in inflammation and pruritus compared to baricitinib and clobetasol. Additionally, skin barrier integrity and epidermal protein expression were improved in IFN‐γ‐iMSC‐EVs. In IL‐4/13‐stimulated keratinocytes, the decrease in JAK1/2 gene expression and the increase in Keratin 1 gene expression were more prominent in IFN‐γ‐iMSC‐EVs than in baricitinib. The results suggest that IFN‐γ‐iMSC‐EVs have the potential to inhibit AD progression and represent a novel therapeutic option for AD.https://doi.org/10.1002/jex2.70067atopic dermatitisextracellular vesiclesIFN‐γmesenchymal stem cellsTh2 immune response
spellingShingle Soo Kim
Jimin Kim
Ran Kim
Hongduk Kim
Seul Ki Lee
Seon‐Yeong Jeong
Haedeun You
Somi Park
Tae Min Kim
iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
Journal of Extracellular Biology
atopic dermatitis
extracellular vesicles
IFN‐γ
mesenchymal stem cells
Th2 immune response
title iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
title_full iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
title_fullStr iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
title_full_unstemmed iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
title_short iMSC‐Derived Extracellular Vesicles Improve Atopic Dermatitis by Augmenting Skin Barrier Integrity and Inhibiting Inflammation, Pruritus and Th2 Immune Responses
title_sort imsc derived extracellular vesicles improve atopic dermatitis by augmenting skin barrier integrity and inhibiting inflammation pruritus and th2 immune responses
topic atopic dermatitis
extracellular vesicles
IFN‐γ
mesenchymal stem cells
Th2 immune response
url https://doi.org/10.1002/jex2.70067
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