Abstract
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.
Highlights
Mesenchymal stem cells (MSCs), the major stem cells in cell therapy, have been used in the clinic for more than 10 years and have proven to be effective for the treatment of various intractable autoimmune and inflammatory disorders because of their distinct immunomodulatory properties [1,2,3,4]
We investigated whether exosomes derived from human umbilical cord mesenchymal stem cells ameliorate psoriasis-like skin inflammation via the IL-23/IL-17 axis
HucMSCs-Exo co-cultured with HaCat cells reduced Signal Transducer and Activator of Transcription 3 (STAT3)/p-STAT3, IL-17, IL-23, and CCL20 levels
Summary
Mesenchymal stem cells (MSCs), the major stem cells in cell therapy, have been used in the clinic for more than 10 years and have proven to be effective for the treatment of various intractable autoimmune and inflammatory disorders because of their distinct immunomodulatory properties [1,2,3,4]. A previous preclinical study demonstrated that allogeneic MSC therapy has a beneficial therapeutic effect in psoriasis [10,11,12]. The immunomodulatory effect of mesenchymal stem cells (MSCs) is mediated by MSCs-derived exosomes (MSCs-exo). MSCs-exo are attractive candidates for use in cell therapy for several inflammatory diseases including psoriasis. We investigated whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCsExo) ameliorate psoriasis-like skin inflammation via the IL-23/IL-17 axis
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