{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:57:30Z","timestamp":1774537050806,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund INTERREG","doi-asserted-by":"publisher","award":["AT-CZ-215"],"award-info":[{"award-number":["AT-CZ-215"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Austrian Research Fund FWF","award":["ESP317-B"],"award-info":[{"award-number":["ESP317-B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: MSCs possess strong immunoregulatory properties and play a central role in maintaining immune homeostasis by limiting inflammatory responses. Their function is highly plastic and influenced by environmental cues, including viral signals. How SARS-CoV-2-derived antigens affect MSC immunoregulation remains incompletely understood. This study aimed to investigate the impact of SARS-CoV-2 peptides on MSC-mediated immune modulation of T-cells. Methods: MSCs were stimulated directly with SARS-CoV-2 spike protein S peptides or cocultured with SARS-CoV-2 peptide-activated T-cells. TLR4 surface expression and receptor downstream signaling were assessed to evaluate pathway activation. MSC immunoregulatory function was analyzed by measuring suppression of TNF-\u03b1 and IFN-\u03b3 expression and induction of CD4+FOXP3+ regulatory T-cells. TLR4 inhibition and lipopolysaccharide (LPS) stimulation were used to examine pathway specificity and interaction. Results: SARS-CoV-2 peptides activated TLR4-associated signaling in MSCs, increasing TLR4 expression and NF-\u03baB phosphorylation. Peptide-treated MSCs showed impaired suppression of pro-inflammatory cytokines and reduced induction of regulatory T-cells. TLR4 inhibition prevented these effects. LPS induced similar effects, while combining LPS and peptide stimulation partially restored physiological T-cell cytokine suppression. Conclusions: SARS-CoV-2 peptides modulate MSC immunoregulatory function on T-cells via TLR4-dependent mechanisms.<\/jats:p>","DOI":"10.3390\/cells15070592","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:48:41Z","timestamp":1774532921000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity"],"prefix":"10.3390","volume":"15","author":[{"given":"Sabrina","family":"Summer","sequence":"first","affiliation":[{"name":"Center for Experimental Medicine, Department for Biomedical Research, University for Continuing Education Krems, 3500 Krems, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann Maximilian","family":"Wolf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sigmund Freud Private University, 1020 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3963-9077","authenticated-orcid":false,"given":"Viktoria","family":"Weber","sequence":"additional","affiliation":[{"name":"Center for Biomedical Technology, Department for Biomedical Research, University for Continuing Education Krems, 3500 Krems, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Department for Biomedical Research, University for Continuing Education Krems, 3500 Krems, Austria"},{"name":"Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3727\/096368915X689622","article-title":"Clinical Trials with Mesenchymal Stem Cells: An Update","volume":"25","author":"Squillaro","year":"2016","journal-title":"Cell Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat. 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