Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Psoriasis-like Skin Inflammation
Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Psoriasis-like Skin Inflammation
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源自人脐带间充质干细胞的外泌体可缓解银屑病样皮肤炎症
DOI：
10.1089/jir.2021.0146
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发表时间：
2022
影响因子：
2.3
通讯作者：
Qing Sun
中科院分区：
文献类型：
--
作者：
Yuli Zhang;Jianjun Yan;Zhengjun Li;Juan Zheng;Qing Sun
间充质干细胞(MSCs)在包括银屑病在内的炎症性疾病中的免疫调节作用已有很好的文献报道。然而，间充质干细胞来源的外切体(MSCs-Exo)在银屑病样皮肤炎症中的作用在很大程度上仍不清楚。本研究旨在探讨MSCs-Exo在银屑病样皮肤炎症中是否起到调节作用。我们发现，皮下注射人脐MSCs-Exo(hucMSCs-Exo)可显著抑制咪喹莫特(Imiquimod)诱导的小鼠表皮的增殖，并降低银屑病面积和严重程度指数(PASI)。HucMSCs-Exo还可减少IL-17、IL-23和趋化因子C-C基序配体20(CCL20)的表达，并抑制IMQ诱导的小鼠皮肤和人角质形成细胞(HaCaT)中信号转导和转录激活因子3(STAT3)的磷酸化。此外，与hucMSCs-Exo体外共培养后，树突状细胞(DC)的成熟和激活受到抑制，IL-23的表达水平降低。这些结果表明hucMSCs-Exo通过调节IL-23和IL-17的表达，抑制DC的成熟和活化，有效地减轻小鼠银屑病样皮肤炎症。我们的数据通过利用hucMSCs-Exo的免疫调节作用，为银屑病提供了一种有前景的治疗方法。
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.