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Human umbilical cord mesenchymal stem cell (MSC)\u2010derived exosomes (hucMSC\u2010Exos) represent a potential cell\u2010free therapeutic strategy, but their mechanisms remain incompletely defined. This study evaluated the effects of hucMSC\u2010Exos in psoriasiform inflammation and investigated the contribution of exosomal miR\u2010125b\u20105p and its relationship with STAT3 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>hucMSC\u2010Exos were isolated by differential ultracentrifugation and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and immunoblotting. Therapeutic effects were assessed in an imiquimod (IMQ)\u2010induced mouse model of psoriasiform dermatitis using PASI\u2010like scoring, histopathology, immunohistochemistry, flow cytometry, and western blotting. Exosomal microRNAs (miRNAs) were profiled by high\u2010throughput sequencing. STAT3 targeting was examined by dual\u2010luciferase reporter assays, and the functional contribution of miR\u2010125b\u20105p was assessed using exosomes loaded with a miR\u2010125b\u20105p inhibitory oligonucleotide and negative\u2010control exosomes (NC\u2010Exos).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>hucMSC\u2010Exos alleviated IMQ\u2010induced psoriasiform dermatitis, as reflected by reduced epidermal hyperplasia and fewer Ki\u201067\u2010positive keratinocytes. Exosome treatment was associated with decreased phosphorylation of STAT3 and JNK, lower IL\u201023 and IL\u201017A expression, decreased Th17\u2010cell frequency, and increased regulatory T cell (Treg)\u2010cell frequency. In vitro, hucMSC\u2010Exos suppressed Th17\u2010cell proliferation while promoting Treg\u2010cell expansion. miR\u2010125b\u20105p was among the abundant miRNAs detected in hucMSC\u2010Exos, and dual\u2010luciferase reporter assays supported STAT3 as a direct target of miR\u2010125b\u20105p. Compared with NC\u2010Exos, inhibitor\u2010loaded exosomes (IN\u2010Exos) were less effective at alleviating IMQ\u2010induced psoriasiform dermatitis; this reduced efficacy was accompanied by increased STAT3 and JNK phosphorylation, higher IL\u201023 and IL\u201017A expression, a higher Th17\u2010cell frequency, and a lower Treg\u2010cell frequency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>hucMSC\u2010Exos attenuated psoriasiform inflammation and were associated with reduced inflammatory signaling, decreased Th17\u2010cell frequency, and increased Treg\u2010cell frequency. Our findings further suggest that exosomal miR\u2010125b\u20105p contributes, at least in part, to these effects through direct regulation of STAT3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/sci\/4935728","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:52:17Z","timestamp":1790337137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Umbilical Cord Mesenchymal Stem Cell\u2010Derived Exosomes Attenuate IMQ\u2010Induced Psoriasiform Dermatitis: A Preclinical Experimental Study of Exosomal miR\u2010125b\u20105p\/STAT3 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