Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways
Immature dendritic cells (DCs) can induce T-cell hyporesponsiveness, thus interfering with the process of DC maturation in a pro-inflammatory context, may therefore provide a novel approach to inducing allograft tolerance. We have studied the effects of mycophenolic acid (MPA), an immunosuppressive...
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| Veröffentlicht in: | International immunology 2005-04, Vol.17 (4), p.351-363 |
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| creator | Lagaraine, Christine Hoarau, Cyrille Chabot, Valérie Velge-Roussel, Florence Lebranchu, Yvon |
| description | Immature dendritic cells (DCs) can induce T-cell hyporesponsiveness, thus interfering with the process of DC maturation in a pro-inflammatory context, may therefore provide a novel approach to inducing allograft tolerance. We have studied the effects of mycophenolic acid (MPA), an immunosuppressive agent currently used in transplantation, using an in vitro model of a mixed human DC/alloreactive CD4+ T lymphocyte culture. DCs differentiated from monocytes were exposed to MPA during maturation. MPA treatment affected the maturation of DCs, and this was reflected both in the impairment of the up-regulation of co-stimulatory molecule expression and the maintained endocytic capacity. However, MPA-DCs exhibited a distinctive microscopic morphology and secreted IL-10 and so could no longer be regarded as immature DC. Moreover, MPA-DCs had a mature phenotype for chemokine receptor expression, exhibiting down-regulation of CCR5 and up-regulation of CCR7. Interestingly, the abilities of the MPA-DCs to induce CD4+ T-cell proliferation in response to alloantigens was impaired not only via direct but also via indirect pathways. The maintenance of endocytosis and the inhibition of syngeneic T-cell activation suggest that these cells could have a potential role to avoid chronic rejection. All these characteristics suggest that MPA-DCs may be used in cell therapy to induce allograft tolerance. |
| doi_str_mv | 10.1093/intimm/dxh215 |
| format | Article |
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We have studied the effects of mycophenolic acid (MPA), an immunosuppressive agent currently used in transplantation, using an in vitro model of a mixed human DC/alloreactive CD4+ T lymphocyte culture. DCs differentiated from monocytes were exposed to MPA during maturation. MPA treatment affected the maturation of DCs, and this was reflected both in the impairment of the up-regulation of co-stimulatory molecule expression and the maintained endocytic capacity. However, MPA-DCs exhibited a distinctive microscopic morphology and secreted IL-10 and so could no longer be regarded as immature DC. Moreover, MPA-DCs had a mature phenotype for chemokine receptor expression, exhibiting down-regulation of CCR5 and up-regulation of CCR7. Interestingly, the abilities of the MPA-DCs to induce CD4+ T-cell proliferation in response to alloantigens was impaired not only via direct but also via indirect pathways. The maintenance of endocytosis and the inhibition of syngeneic T-cell activation suggest that these cells could have a potential role to avoid chronic rejection. All these characteristics suggest that MPA-DCs may be used in cell therapy to induce allograft tolerance.</description><identifier>ISSN: 0953-8178</identifier><identifier>EISSN: 1460-2377</identifier><identifier>DOI: 10.1093/intimm/dxh215</identifier><identifier>PMID: 15710908</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>2′-O-dibutyrylguanosine 3 ; 5′-cyclic monophosphate sodium salt ; 5′-cyclic monophosphorothioate triethylammonium salt ; APC antigen-presenting cells ; Apoptosis - drug effects ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cell therapy ; dbGMPc N-2 ; DC dendritic cell ; Dendritic Cells - drug effects ; Dendritic Cells - enzymology ; Dendritic Cells - immunology ; EFS Etablissement Français du Sang ; GAPDH glyseraldehyde-3 phosphate dehydrogenase ; GM-CSF granulocyte macrophage colony-stimulating factor ; HSA human serum albumin ; Humans ; Immunosuppressive agent ; IMP Dehydrogenase - antagonists & inhibitors ; IMPDH inosine monophosphate dehydrogenase ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; MFI mean fluorescence intensity ; MLR mixed leukocyte reaction ; MMF mycophenolate mofetil ; MPA mycophenolic acid ; Mycophenolic Acid - pharmacology ; poly I:C polyinosine-polycytidylic acid ; Rp-AMPS Rp-adenosine 3 ; RPA RNase protection assay ; TLR Toll-like receptor ; TNF-α tumor necrosis factor-α ; Tolerance ; Transplantation</subject><ispartof>International immunology, 2005-04, Vol.17 (4), p.351-363</ispartof><rights>Copyright Oxford University Press(England) Apr 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-fa863196779d6fd1b1a1f9a0ff2ac269c9670d8efa79e9d9e986a47eaae0ab803</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15710908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lagaraine, Christine</creatorcontrib><creatorcontrib>Hoarau, Cyrille</creatorcontrib><creatorcontrib>Chabot, Valérie</creatorcontrib><creatorcontrib>Velge-Roussel, Florence</creatorcontrib><creatorcontrib>Lebranchu, Yvon</creatorcontrib><title>Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways</title><title>International immunology</title><addtitle>Int. Immunol</addtitle><description>Immature dendritic cells (DCs) can induce T-cell hyporesponsiveness, thus interfering with the process of DC maturation in a pro-inflammatory context, may therefore provide a novel approach to inducing allograft tolerance. We have studied the effects of mycophenolic acid (MPA), an immunosuppressive agent currently used in transplantation, using an in vitro model of a mixed human DC/alloreactive CD4+ T lymphocyte culture. DCs differentiated from monocytes were exposed to MPA during maturation. MPA treatment affected the maturation of DCs, and this was reflected both in the impairment of the up-regulation of co-stimulatory molecule expression and the maintained endocytic capacity. However, MPA-DCs exhibited a distinctive microscopic morphology and secreted IL-10 and so could no longer be regarded as immature DC. Moreover, MPA-DCs had a mature phenotype for chemokine receptor expression, exhibiting down-regulation of CCR5 and up-regulation of CCR7. Interestingly, the abilities of the MPA-DCs to induce CD4+ T-cell proliferation in response to alloantigens was impaired not only via direct but also via indirect pathways. The maintenance of endocytosis and the inhibition of syngeneic T-cell activation suggest that these cells could have a potential role to avoid chronic rejection. All these characteristics suggest that MPA-DCs may be used in cell therapy to induce allograft tolerance.</description><subject>2′-O-dibutyrylguanosine 3</subject><subject>5′-cyclic monophosphate sodium salt</subject><subject>5′-cyclic monophosphorothioate triethylammonium salt</subject><subject>APC antigen-presenting cells</subject><subject>Apoptosis - drug effects</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell therapy</subject><subject>dbGMPc N-2</subject><subject>DC dendritic cell</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - enzymology</subject><subject>Dendritic Cells - immunology</subject><subject>EFS Etablissement Français du Sang</subject><subject>GAPDH glyseraldehyde-3 phosphate dehydrogenase</subject><subject>GM-CSF granulocyte macrophage colony-stimulating factor</subject><subject>HSA human serum albumin</subject><subject>Humans</subject><subject>Immunosuppressive agent</subject><subject>IMP Dehydrogenase - antagonists & inhibitors</subject><subject>IMPDH inosine monophosphate dehydrogenase</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>MFI mean fluorescence intensity</subject><subject>MLR mixed leukocyte reaction</subject><subject>MMF mycophenolate mofetil</subject><subject>MPA mycophenolic acid</subject><subject>Mycophenolic Acid - pharmacology</subject><subject>poly I:C polyinosine-polycytidylic acid</subject><subject>Rp-AMPS Rp-adenosine 3</subject><subject>RPA RNase protection assay</subject><subject>TLR Toll-like receptor</subject><subject>TNF-α tumor necrosis factor-α</subject><subject>Tolerance</subject><subject>Transplantation</subject><issn>0953-8178</issn><issn>1460-2377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhyBVZHLiF2nEcx0eoKEXqigMgIS7WbDxpXBIn2E5pfgd_GC-7ohIXDpZlvW_e6PkR8pyz15xpceZ8cuN4Zu_6kssHZMOrmhWlUOoh2TAtRdFw1ZyQJzHeMMZEqcVjcsKlysOs2ZBf27Wd5h79NLiWQutskQJCQkv7ZQRPLXobXMpii8MQaQ-3SIGOkJaAdHTXAdIUVvrHI61zFr2lzvdu5xKFYZiu0WMeDxjnyUeM9NYBtS5gm47s8TFD6n_CGp-SRx0MEZ8d71Py5eLd5_PL4urj-w_nb66KtpIyFR00teC6VkrburN8x4F3GljXldCWtW6zxGyDHSiN2ubT1FApBEAGu4aJU_Lq4DuH6ceCMZnRxX1K8Dgt0dRKSl5W1X_B_MOsZrzO4Mt_wJtpCT6HMFxLJhrJ92uLA9SGKcaAnZmDGyGshjOz79QcOjWHTjP_4mi67Ea09_SxxHtDFxPe_dUhfM8RhJLm8us3c_FWbHW1_WSY-A1IMLIQ</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Lagaraine, Christine</creator><creator>Hoarau, Cyrille</creator><creator>Chabot, Valérie</creator><creator>Velge-Roussel, Florence</creator><creator>Lebranchu, Yvon</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways</title><author>Lagaraine, Christine ; Hoarau, Cyrille ; Chabot, Valérie ; Velge-Roussel, Florence ; Lebranchu, Yvon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-fa863196779d6fd1b1a1f9a0ff2ac269c9670d8efa79e9d9e986a47eaae0ab803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>2′-O-dibutyrylguanosine 3</topic><topic>5′-cyclic monophosphate sodium salt</topic><topic>5′-cyclic monophosphorothioate triethylammonium salt</topic><topic>APC antigen-presenting cells</topic><topic>Apoptosis - drug effects</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell therapy</topic><topic>dbGMPc N-2</topic><topic>DC dendritic cell</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - enzymology</topic><topic>Dendritic Cells - immunology</topic><topic>EFS Etablissement Français du Sang</topic><topic>GAPDH glyseraldehyde-3 phosphate dehydrogenase</topic><topic>GM-CSF granulocyte macrophage colony-stimulating factor</topic><topic>HSA human serum albumin</topic><topic>Humans</topic><topic>Immunosuppressive agent</topic><topic>IMP Dehydrogenase - antagonists & inhibitors</topic><topic>IMPDH inosine monophosphate dehydrogenase</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>MFI mean fluorescence intensity</topic><topic>MLR mixed leukocyte reaction</topic><topic>MMF mycophenolate mofetil</topic><topic>MPA mycophenolic acid</topic><topic>Mycophenolic Acid - pharmacology</topic><topic>poly I:C polyinosine-polycytidylic acid</topic><topic>Rp-AMPS Rp-adenosine 3</topic><topic>RPA RNase protection assay</topic><topic>TLR Toll-like receptor</topic><topic>TNF-α tumor necrosis factor-α</topic><topic>Tolerance</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lagaraine, Christine</creatorcontrib><creatorcontrib>Hoarau, Cyrille</creatorcontrib><creatorcontrib>Chabot, Valérie</creatorcontrib><creatorcontrib>Velge-Roussel, Florence</creatorcontrib><creatorcontrib>Lebranchu, Yvon</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lagaraine, Christine</au><au>Hoarau, Cyrille</au><au>Chabot, Valérie</au><au>Velge-Roussel, Florence</au><au>Lebranchu, Yvon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways</atitle><jtitle>International immunology</jtitle><addtitle>Int. Immunol</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>17</volume><issue>4</issue><spage>351</spage><epage>363</epage><pages>351-363</pages><issn>0953-8178</issn><eissn>1460-2377</eissn><abstract>Immature dendritic cells (DCs) can induce T-cell hyporesponsiveness, thus interfering with the process of DC maturation in a pro-inflammatory context, may therefore provide a novel approach to inducing allograft tolerance. We have studied the effects of mycophenolic acid (MPA), an immunosuppressive agent currently used in transplantation, using an in vitro model of a mixed human DC/alloreactive CD4+ T lymphocyte culture. DCs differentiated from monocytes were exposed to MPA during maturation. MPA treatment affected the maturation of DCs, and this was reflected both in the impairment of the up-regulation of co-stimulatory molecule expression and the maintained endocytic capacity. However, MPA-DCs exhibited a distinctive microscopic morphology and secreted IL-10 and so could no longer be regarded as immature DC. Moreover, MPA-DCs had a mature phenotype for chemokine receptor expression, exhibiting down-regulation of CCR5 and up-regulation of CCR7. Interestingly, the abilities of the MPA-DCs to induce CD4+ T-cell proliferation in response to alloantigens was impaired not only via direct but also via indirect pathways. The maintenance of endocytosis and the inhibition of syngeneic T-cell activation suggest that these cells could have a potential role to avoid chronic rejection. All these characteristics suggest that MPA-DCs may be used in cell therapy to induce allograft tolerance.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>15710908</pmid><doi>10.1093/intimm/dxh215</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 2′-O-dibutyrylguanosine 3 5′-cyclic monophosphate sodium salt 5′-cyclic monophosphorothioate triethylammonium salt APC antigen-presenting cells Apoptosis - drug effects Cell Movement - drug effects Cell Proliferation - drug effects Cell therapy dbGMPc N-2 DC dendritic cell Dendritic Cells - drug effects Dendritic Cells - enzymology Dendritic Cells - immunology EFS Etablissement Français du Sang GAPDH glyseraldehyde-3 phosphate dehydrogenase GM-CSF granulocyte macrophage colony-stimulating factor HSA human serum albumin Humans Immunosuppressive agent IMP Dehydrogenase - antagonists & inhibitors IMPDH inosine monophosphate dehydrogenase Lymphocyte Activation - drug effects Lymphocyte Activation - immunology MFI mean fluorescence intensity MLR mixed leukocyte reaction MMF mycophenolate mofetil MPA mycophenolic acid Mycophenolic Acid - pharmacology poly I:C polyinosine-polycytidylic acid Rp-AMPS Rp-adenosine 3 RPA RNase protection assay TLR Toll-like receptor TNF-α tumor necrosis factor-α Tolerance Transplantation |
| title | Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways |
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