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Int. J. Mol. Sci. 2018, 19(8), 2312;

CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells

Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, 10117 Berlin, Germany
Department of Orthopedics, Campus Eisenberg, Jena University Hospital, Klosterlausnitzer Straße 81, 07607 Eisenberg, Germany
Endokrinologikum Berlin, 10117 Berlin, Germany
Authors to whom correspondence should be addressed.
Received: 28 June 2018 / Revised: 1 August 2018 / Accepted: 2 August 2018 / Published: 7 August 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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. View Full-Text
Keywords: mesenchymal stem/stromal cells; immune modulation; CTLA-4; hypoxia; fracture healing; regeneration mesenchymal stem/stromal cells; immune modulation; CTLA-4; hypoxia; fracture healing; regeneration

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Gaber, T.; Schönbeck, K.; Hoff, H.; Tran, C.L.; Strehl, C.; Lang, A.; Ohrndorf, S.; Pfeiffenberger, M.; Röhner, E.; Matziolis, G.; Burmester, G.-R.; Buttgereit, F.; Hoff, P. CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells. Int. J. Mol. Sci. 2018, 19, 2312.

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