{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:11:14Z","timestamp":1788779474060,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hidradenitis suppurativa is a chronic inflammatory skin disease marked by immune dysregulation and elevated pro-inflammatory cytokines. While biologics like adalimumab target specific pathways, their limited efficacy highlights the need for broader immunomodulatory treatments. Mesenchymal stem\/stromal cells (MSCs) have shown promise due to their immunosuppressive properties and ability to modulate both innate and adaptive immunity. This study investigates the effects of na\u00efve (n-MSCs) and cytokine-preactivated (a-MSCs) placental MSCs on the immune responses in HS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MSCs were isolated from healthy term placentas and either used na\u00efvely or preactivated with IFN-\u03b3 and TNF-\u03b1. Peripheral blood mononuclear cells (PBMCs) from HS patients (n=3) and healthy donors (n=3) were co-cultured with n-MSCs, a-MSCs, or adalimumab. Additionally, lesional, perilesional, and healthy 4 mm in diameter skin punch biopsies from 10 HS patients and 3 controls were cultured in a transwell system with the same interventions. Flow cytometry assessed lymphocytes proliferation and T cell subsets while Luminex assays measured cytokine levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both n-MSCs and a-MSCs significantly inhibited lymphocytes proliferation and shifted T cell populations, increasing CD4+ and decreasing CD8+ T cells. The a-MSCs notably reduced IL-17A and IFN-\u03b3 in PBMC co-cultures; n-MSCs had partial effects. HS skin explants exhibited elevated IL-1\u03b2, IL-10, and IL-17A compared to healthy skin. The n-MSCs markedly reduced all three cytokines in lesional and perilesional tissues. Moreover, a-MSCs selectively increased IL-10 in lesional skin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Placental MSCs, especially in their na\u00efve form, demonstrate potent immunomodulatory effects by reducing pro-inflammatory cytokines and altering T cell dynamics in HS. Compared to adalimumab, MSCs offer a broader immunoregulatory profile, suggesting their potential as a multitarget therapy for HS. These findings support further clinical investigation of MSC-based treatments in managing this complex disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1642014","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:18:26Z","timestamp":1758773906000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro and ex vivo immunomodulatory effects of human placental mesenchymal stem cells in hidradenitis 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