Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells

Background Bone marrow‐derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect and therefore may have a therapeutic potential in T‐cell‐dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involve...

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Veröffentlicht in:Clinical transplantation 2018-04, Vol.32 (4), p.e13231-n/a
Hauptverfasser: Hua, Fei, Chen, Yueqiu, Yang, Ziying, Teng, Xiaomei, Huang, Haoyue, Shen, Zhenya
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container_end_page n/a
container_issue 4
container_start_page e13231
container_title Clinical transplantation
container_volume 32
creator Hua, Fei
Chen, Yueqiu
Yang, Ziying
Teng, Xiaomei
Huang, Haoyue
Shen, Zhenya
description Background Bone marrow‐derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect and therefore may have a therapeutic potential in T‐cell‐dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). Methods Bone marrow‐derived DCs and BMSCs were co‐cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT‐PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL‐10. Survival time of transplanted heart and expression of CD4+, CD8+, IL‐2, IL‐4, IL‐10, IFN‐γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results DCs co‐cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB+ DCs co‐cultured with T‐cells CD4+ displayed increased T‐cell CD4+ Foxp3 ratio and IL‐10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4+, expression levels of IL‐2 and IFN‐γ, and increased the CD4+ Foxp3 ratio and levels of IL‐4 and IL‐10. CD45RB+ DCs achieved better protective effects than DCs. Conclusion BMSCs increased the expression of CD45RB in the bone marrow‐derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.
doi_str_mv 10.1111/ctr.13231
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We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). Methods Bone marrow‐derived DCs and BMSCs were co‐cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT‐PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL‐10. Survival time of transplanted heart and expression of CD4+, CD8+, IL‐2, IL‐4, IL‐10, IFN‐γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results DCs co‐cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB+ DCs co‐cultured with T‐cells CD4+ displayed increased T‐cell CD4+ Foxp3 ratio and IL‐10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4+, expression levels of IL‐2 and IFN‐γ, and increased the CD4+ Foxp3 ratio and levels of IL‐4 and IL‐10. CD45RB+ DCs achieved better protective effects than DCs. Conclusion BMSCs increased the expression of CD45RB in the bone marrow‐derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.</description><identifier>ISSN: 0902-0063</identifier><identifier>EISSN: 1399-0012</identifier><identifier>DOI: 10.1111/ctr.13231</identifier><identifier>PMID: 29488658</identifier><language>eng</language><publisher>Denmark</publisher><subject>allogeneic heart transplantation ; bone marrow mesenchymal stem cell ; CD4 ; CD8 ; dendritic cell ; immune tolerance</subject><ispartof>Clinical transplantation, 2018-04, Vol.32 (4), p.e13231-n/a</ispartof><rights>2018 John Wiley &amp; Sons A/S. 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We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). Methods Bone marrow‐derived DCs and BMSCs were co‐cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT‐PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL‐10. Survival time of transplanted heart and expression of CD4+, CD8+, IL‐2, IL‐4, IL‐10, IFN‐γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results DCs co‐cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB+ DCs co‐cultured with T‐cells CD4+ displayed increased T‐cell CD4+ Foxp3 ratio and IL‐10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4+, expression levels of IL‐2 and IFN‐γ, and increased the CD4+ Foxp3 ratio and levels of IL‐4 and IL‐10. CD45RB+ DCs achieved better protective effects than DCs. Conclusion BMSCs increased the expression of CD45RB in the bone marrow‐derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.</description><subject>allogeneic heart transplantation</subject><subject>bone marrow mesenchymal stem cell</subject><subject>CD4</subject><subject>CD8</subject><subject>dendritic cell</subject><subject>immune tolerance</subject><issn>0902-0063</issn><issn>1399-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNo9kdtOAyEQhonRaK1e-AKGSxPTlsOeuNR6TJpomnq9YZfZuoaFCqxNH8T3ldYqNzPDfPND5kfogpIxjWdSBzemnHF6gAaUCzEihLJDNCCCsJhn_ASdev8RbzOapcfohImkKLK0GKDvV2cD1KH9AixjsAbbBlfWAO6kc3aNO_Bg6vdNJzX2ATpcg9Yetwa3XddHLlgNTpoatpNSa7sEA22N30G6gENs-ZWWJsiderXBDpa9jpVZ4uldks5vr7ECo1wb4tRO_QwdNVJ7ON_HIXp7uF9Mn0azl8fn6c1stGIppaNUqaahWcEU55DTSikBlHOimkpkaSMLkiey4iwXOdC6EKzJiyQReU1lrkDkfIiufnVXzn724EPZtX77A2nA9r5khAhG41Nb9HKP9lUHqly5Ni5oU_6tMgKTX2Ddatj89ykptx6V0aNy51E5Xcx3Cf8B3Q-GIQ</recordid><startdate>201804</startdate><enddate>201804</enddate><creator>Hua, Fei</creator><creator>Chen, Yueqiu</creator><creator>Yang, Ziying</creator><creator>Teng, Xiaomei</creator><creator>Huang, Haoyue</creator><creator>Shen, Zhenya</creator><scope>NPM</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8221-9628</orcidid></search><sort><creationdate>201804</creationdate><title>Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells</title><author>Hua, Fei ; Chen, Yueqiu ; Yang, Ziying ; Teng, Xiaomei ; Huang, Haoyue ; Shen, Zhenya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2511-5ddff1682d33e71bdd9e1330dfb965fa8074ab32797e1c892f784497c1a7de973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>allogeneic heart transplantation</topic><topic>bone marrow mesenchymal stem cell</topic><topic>CD4</topic><topic>CD8</topic><topic>dendritic cell</topic><topic>immune tolerance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hua, Fei</creatorcontrib><creatorcontrib>Chen, Yueqiu</creatorcontrib><creatorcontrib>Yang, Ziying</creatorcontrib><creatorcontrib>Teng, Xiaomei</creatorcontrib><creatorcontrib>Huang, Haoyue</creatorcontrib><creatorcontrib>Shen, Zhenya</creatorcontrib><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hua, Fei</au><au>Chen, Yueqiu</au><au>Yang, Ziying</au><au>Teng, Xiaomei</au><au>Huang, Haoyue</au><au>Shen, Zhenya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells</atitle><jtitle>Clinical transplantation</jtitle><addtitle>Clin Transplant</addtitle><date>2018-04</date><risdate>2018</risdate><volume>32</volume><issue>4</issue><spage>e13231</spage><epage>n/a</epage><pages>e13231-n/a</pages><issn>0902-0063</issn><eissn>1399-0012</eissn><abstract>Background Bone marrow‐derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect and therefore may have a therapeutic potential in T‐cell‐dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). Methods Bone marrow‐derived DCs and BMSCs were co‐cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT‐PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL‐10. Survival time of transplanted heart and expression of CD4+, CD8+, IL‐2, IL‐4, IL‐10, IFN‐γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results DCs co‐cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB+ DCs co‐cultured with T‐cells CD4+ displayed increased T‐cell CD4+ Foxp3 ratio and IL‐10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4+, expression levels of IL‐2 and IFN‐γ, and increased the CD4+ Foxp3 ratio and levels of IL‐4 and IL‐10. CD45RB+ DCs achieved better protective effects than DCs. Conclusion BMSCs increased the expression of CD45RB in the bone marrow‐derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.</abstract><cop>Denmark</cop><pmid>29488658</pmid><doi>10.1111/ctr.13231</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8221-9628</orcidid></addata></record>
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subjects allogeneic heart transplantation
bone marrow mesenchymal stem cell
CD4
CD8
dendritic cell
immune tolerance
title Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells
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