The pathogenesis of atopic dermatitis (AD) is multifactorial, including immune dysregulation and epidermal barrier defects, and a novel therapeutic modality that can simultaneously target multiple pathways is needed. We investigated the therapeutic effects of exosomes (IFN-γ-iExo) secreted from IFN-γ-primed induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) in mice with Aspergillus fumigatus-induced AD. IFN-γ-iExo was epicutaneously administered to mice with AD-like skin lesions. The effects of IFN-γ-iExo treatment were investigated through clinical scores, transepidermal water loss (TEWL) measurements, and histopathology. To elucidate the therapeutic mechanism, we used an in vitro model of human keratinocyte HaCaT cells stimulated with IL-4 and IL-13 and performed extensive bioinformatics analysis of skin mRNA from mice. The expression of indoleamine 2,3-dioxygenase was higher in IFN-γ primed iMSCs than in iMSCs. In human keratinocyte HaCaT cells, treatment with IFN-γ-iExo led to decreases in the mRNA expression of thymic stromal lymphopoietin, IL-25, and IL-33 and increases in keratin 1, keratin 10, desmoglein 1, and ceramide synthase 3. IFN-γ-iExo treatment significantly improved clinical and histological outcomes in AD mice, including clinical scores, TEWL, inflammatory cell infiltration, and epidermal thickness. Bioinformatics analysis of skin mRNA from AD mice showed that IFN-γ-iExo treatment is predominantly involved in skin barrier function and T cell immune response. Treatment with IFN-γ-iExo improved the clinical and histological outcomes of AD mice, which were likely mediated by restoring proper skin barrier function and suppressing T cell-mediated immune response.

Gyun-Sik Oh, Si-Ryong Kim , Eun-Sook Lee, Jin Yoon, Min-Kyung Shin, Hyeon Kyoung Ryu, Dong Seop Kim, and Seung-Whan Kim. Mol. Cells 2022;45:180-92. https://doi.org/10.14348/molcells.2022.2222

Park A, et al. J Korean Med Sci. 2021 Sep;36(40):e261. https://doi.org/10.3346/jkms.2021.36.e261

Song N, et al. Korean Circ J. 2025 Sep;56:e4. https://doi.org/10.4070/kcj.2025.0137

Yoon J, et al. J Korean Med Sci. 2024 Jul;39:e221. https://doi.org/10.3346/jkms.2024.39.e221