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

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 p...

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Bibliographic Details
Published in:International journal of molecular sciences 2018-08, Vol.19 (8), p.2312
Main Authors: Gaber, Timo, Schönbeck, Kerstin, Hoff, Holger, Tran, Cam Loan, Strehl, Cindy, Lang, Annemarie, Ohrndorf, Sarah, Pfeiffenberger, Moritz, Röhner, Eric, Matziolis, Georg, Burmester, Gerd-R, Buttgereit, Frank, Hoff, Paula
Format: Article
Language:English
Subjects:
Adipogenesis
Autoimmune diseases
Bone healing
Cartilage
Cells, Cultured
CTLA-4 Antigen - analysis
CTLA-4 Antigen - immunology
CTLA-4 protein
Cytotoxicity
Environmental conditions
Healing
Humans
Hypoxia
Immune response
Immune Tolerance
Immunomodulation
Immunosuppression
Isoforms
Lymphocytes T
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - immunology
Mesenchyme
Osteogenesis
Phenotypes
Stem cells
Stromal cells
Tissue engineering
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19082312