Extracellular vesicles from IFN-[gamma]-primed mesenchymal stem cells repress atopic dermatitis in mice

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as...

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Published inJournal of nanobiotechnology Vol. 20; no. 1
Main Authors Kim, Jimin, Lee, Seul Ki, Jung, Minyoung, Jeong, Seon-Yeong, You, Haedeun, Won, Ji-Yeon, Han, Sang-Deok, Cho, Hye Jin, Park, Somi, Park, Joonghoon, Kim, Tae Min, Kim, Soo
Format Journal Article
LanguageEnglish
Published BioMed Central Ltd 10.12.2022
Subjects
Atopic dermatitis
Care and treatment
Cell organelles
Cellular therapy
Health aspects
Interferon gamma
Methods
Stem cells
South Korea
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Summary:Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. Proteome analysis showed that IFN-[gamma]-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4R[alpha]/13R[alpha]1/31R[alpha]) and activation of their corresponding intracellular signaling molecules was reduced. IFN-[gamma]-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. IFN-[gamma]-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.
ISSN:1477-3155
1477-3155
DOI:10.1186/s12951-022-01728-8