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<p>The immunomodulatory effects and therapeutic potential of human umbilical cord-derived mesenchymal stem cell exosomes (MSCexo) are well established. However, the impact of MSCexo on non-immune cell subsets is not fully understood. In this study, imiquimod (IMQ)-induced psoriasis-like skin inflammation was used to elucidate the alleviating effects of MSCexo. Through single-cell transcriptome sequencing, we identified that MSCexo modulates two subsets of keratinocytes (KCs) characterized by high expression of of IgGFc-binding protein (Fcgbp) or Pleiotrophin (Ptn). KC2 (<i>Fcgbp</i><sup>+</sup> KCs) are considered as the progenitors of terminally differentiated keratinocytes, characterized by their robust proliferative capacity. Cellular communication and transcription factor network analysis suggests that MSCexo may regulate the differentiation of KC2 (<i>Fcgbp</i><sup>+</sup> KCs) into KC5 (<i>Ptn</i><sup>+</sup> KCs) via the activating transcription factor 3 (ATF3) -trigged axis. By employing the ATF3 inducer achiral 7-methoxy-3-methyl-1&#xa0;H-chromeno[4,3-c]pyrazol-4-one in IMQ-mouse model, we have demonstrated the inhibitory effect of ATF3 on keratinocyte differentiation and homeostasis. Our findings reveal that MSCexo alleviates imiquimod-induced psoriasis-like dermatitis by modulating ATF3-induced keratinocyte differentiation, thereby proposing the MSCexo-ATF3-keratinocyte axis as a targeted therapeutic strategy against psoriatic pathology.</p>

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Mesenchymal stem cells-derived exosome relieves imiquimod-induced psoriasis‐like dermatitis by targeting keratinocyte differentiation

  • 期刊论文

  • 发表日期：

    2026年2月28日

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  • Ying Fu,
  • Yue Gao,
  • Qiang Guo,
  • Mengwei Fu,
  • Yixin Yan,
  • Yunge Wang,
  • Xuan Dong

摘要

The immunomodulatory effects and therapeutic potential of human umbilical cord-derived mesenchymal stem cell exosomes (MSCexo) are well established. However, the impact of MSCexo on non-immune cell subsets is not fully understood. In this study, imiquimod (IMQ)-induced psoriasis-like skin inflammation was used to elucidate the alleviating effects of MSCexo. Through single-cell transcriptome sequencing, we identified that MSCexo modulates two subsets of keratinocytes (KCs) characterized by high expression of of IgGFc-binding protein (Fcgbp) or Pleiotrophin (Ptn). KC2 (Fcgbp+ KCs) are considered as the progenitors of terminally differentiated keratinocytes, characterized by their robust proliferative capacity. Cellular communication and transcription factor network analysis suggests that MSCexo may regulate the differentiation of KC2 (Fcgbp+ KCs) into KC5 (Ptn+ KCs) via the activating transcription factor 3 (ATF3) -trigged axis. By employing the ATF3 inducer achiral 7-methoxy-3-methyl-1 H-chromeno[4,3-c]pyrazol-4-one in IMQ-mouse model, we have demonstrated the inhibitory effect of ATF3 on keratinocyte differentiation and homeostasis. Our findings reveal that MSCexo alleviates imiquimod-induced psoriasis-like dermatitis by modulating ATF3-induced keratinocyte differentiation, thereby proposing the MSCexo-ATF3-keratinocyte axis as a targeted therapeutic strategy against psoriatic pathology.