Immunomodulatory effects of mesenchymal stem cells (MSCs) in inflammatory diseases, including psoriasis, are well documented. However, the role of MSC-derived exosomes (MSCs-Exo) in psoriasis-like skin inflammation remains largely unknown. This study aimed to investigate whether MSCs-Exo play a regulatory role in psoriasis-like skin inflammation. We found that subcutaneous injection of human umbilical cord MSCs-Exo (hucMSCs-Exo) significantly suppressed the proliferation of epidermis and reduced Psoriasis Area and Severity Index (PASI) scores in imiquimod (IMQ)-induced mice. hucMSCs-Exo also reduced the expression of interleukin (IL)-17, IL-23, and chemokine C-C-motif ligand 20 (CCL20) and inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the skin of IMQ-induced mice and in human keratinocyte (HaCaT) cells. In addition, co-cultured with hucMSCs-Exo in vitro, the maturation and activation of dendritic cells (DCs) were suppressed, and the expression level of IL-23 was decreased. These results indicate that hucMSCs-Exo can effectively ameliorate psoriasis-like skin inflammation in mice by regulating the expression of IL-23 and IL-17, and inhibiting the maturation and activation of DCs. Our data offer a promising therapeutic approach for psoriasis by leveraging the immunomodulatory effects of hucMSCs-Exo.
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