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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| Veröffentlicht in: | International journal of molecular sciences 2018-08, Vol.19 (8), p.2312 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.3390/ijms19082312 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms19082312</identifier><identifier>PMID: 30087255</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>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</subject><ispartof>International journal of molecular sciences, 2018-08, Vol.19 (8), p.2312</ispartof><rights>2018. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-bee67e8eb33f34ae8ffd9e6c083489ceb998e599f00774c83068aae47f1307f23</citedby><cites>FETCH-LOGICAL-c478t-bee67e8eb33f34ae8ffd9e6c083489ceb998e599f00774c83068aae47f1307f23</cites><orcidid>0000-0002-5105-5875 ; 0000-0002-6675-3895</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121442/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121442/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30087255$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaber, Timo</creatorcontrib><creatorcontrib>Schönbeck, Kerstin</creatorcontrib><creatorcontrib>Hoff, Holger</creatorcontrib><creatorcontrib>Tran, Cam Loan</creatorcontrib><creatorcontrib>Strehl, Cindy</creatorcontrib><creatorcontrib>Lang, Annemarie</creatorcontrib><creatorcontrib>Ohrndorf, Sarah</creatorcontrib><creatorcontrib>Pfeiffenberger, Moritz</creatorcontrib><creatorcontrib>Röhner, Eric</creatorcontrib><creatorcontrib>Matziolis, Georg</creatorcontrib><creatorcontrib>Burmester, Gerd-R</creatorcontrib><creatorcontrib>Buttgereit, Frank</creatorcontrib><creatorcontrib>Hoff, Paula</creatorcontrib><title>CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>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.</description><subject>Adipogenesis</subject><subject>Autoimmune diseases</subject><subject>Bone healing</subject><subject>Cartilage</subject><subject>Cells, Cultured</subject><subject>CTLA-4 Antigen - analysis</subject><subject>CTLA-4 Antigen - immunology</subject><subject>CTLA-4 protein</subject><subject>Cytotoxicity</subject><subject>Environmental conditions</subject><subject>Healing</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immune response</subject><subject>Immune Tolerance</subject><subject>Immunomodulation</subject><subject>Immunosuppression</subject><subject>Isoforms</subject><subject>Lymphocytes T</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - immunology</subject><subject>Mesenchyme</subject><subject>Osteogenesis</subject><subject>Phenotypes</subject><subject>Stem cells</subject><subject>Stromal cells</subject><subject>Tissue engineering</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1rGzEQxUVoqfN1y7ks9NJDNxl97Eq6FIJJ0oBLDnbOQiuPapndVSrtFvzfd43T4OY0M8yPx7x5hFxRuOZcw03YdplqUIxTdkJOqWCsBKjlh6N-Rs5y3gIwzir9icw4gJKsqk7J3Xy1uC1F8RPXwQ6Yi8d-E5owxLQr7sfeDSH2RfTTPmPvNrvOtsVywO5mOaS4H-bYtvmCfPS2zXj5Ws_J8_3dav6jXDw9PM5vF6UTUg1lg1hLVNhw7rmwqLxfa6wdKC6UdthorbDS2gNIKZziUCtrUUhPOUjP-Dn5ftB9GZsO1w77IdnWvKTQ2bQz0Qbz_6YPG_Mr_jE1ZVSIvcDXV4EUf4-YB9OF7CYLtsc4ZsNAVXU1vVVO6Jd36DaOqZ_sGUZBKaaAqYn6dqBcijkn9G_HUDD7fMxxPhP--djAG_wvEP4XPSCLLA</recordid><startdate>20180807</startdate><enddate>20180807</enddate><creator>Gaber, Timo</creator><creator>Schönbeck, Kerstin</creator><creator>Hoff, Holger</creator><creator>Tran, Cam Loan</creator><creator>Strehl, Cindy</creator><creator>Lang, Annemarie</creator><creator>Ohrndorf, Sarah</creator><creator>Pfeiffenberger, Moritz</creator><creator>Röhner, Eric</creator><creator>Matziolis, Georg</creator><creator>Burmester, Gerd-R</creator><creator>Buttgereit, Frank</creator><creator>Hoff, Paula</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5105-5875</orcidid><orcidid>https://orcid.org/0000-0002-6675-3895</orcidid></search><sort><creationdate>20180807</creationdate><title>CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-bee67e8eb33f34ae8ffd9e6c083489ceb998e599f00774c83068aae47f1307f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipogenesis</topic><topic>Autoimmune diseases</topic><topic>Bone healing</topic><topic>Cartilage</topic><topic>Cells, Cultured</topic><topic>CTLA-4 Antigen - 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| 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 |
| title | CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells |
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