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- Title
Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice.
- 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
- Abstract
Background: 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. Results: Proteome analysis showed that IFN-γ-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-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-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. Conclusions: IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.
- Subjects
FILAGGRIN; MESENCHYMAL stem cells; EXTRACELLULAR vesicles; KERATINOCYTE differentiation; ATOPIC dermatitis; THYMIC stromal lymphopoietin; PROTEOMICS
- Publication
Journal of Nanobiotechnology, 2022, Vol 20, Issue 1, p1
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/s12951-022-01728-8