{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:12:29Z","timestamp":1790190749596,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T00:00:00Z","timestamp":1533600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["IM101-501_Hoff"],"award-info":[{"award-number":["IM101-501_Hoff"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem\/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic\/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration\/fracture healing is difficult.<\/jats:p>","DOI":"10.3390\/ijms19082312","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T11:20:23Z","timestamp":1533640823000},"page":"2312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem\/Stromal Cells"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-3895","authenticated-orcid":false,"given":"Timo","family":"Gaber","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Sch\u00f6nbeck","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hoff","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cam Loan","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Strehl","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ohrndorf","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Pfeiffenberger","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"R\u00f6hner","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Campus Eisenberg, Jena University Hospital, Klosterlausnitzer Stra\u00dfe 81, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5875","authenticated-orcid":false,"given":"Georg","family":"Matziolis","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Campus Eisenberg, Jena University Hospital, Klosterlausnitzer Stra\u00dfe 81, 07607 Eisenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd-R.","family":"Burmester","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Buttgereit","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany"},{"name":"Department of Orthopedics, Campus Eisenberg, Jena University Hospital, Klosterlausnitzer Stra\u00dfe 81, 07607 Eisenberg, Germany"},{"name":"Endokrinologikum Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,7]]},"reference":[{"key":"ref_1","first-page":"53","article-title":"Resetting the immune system with immunoablation and autologous haematopoietic stem cell transplantation in autoimmune diseases","volume":"34","author":"Alexander","year":"2016","journal-title":"Clin. 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