Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes
Aims/hypothesis Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodu...
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| Veröffentlicht in: | Diabetologia 2014-08, Vol.57 (8), p.1664-1673 |
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| creator | Favaro, Enrica Carpanetto, Andrea Lamorte, Sara Fusco, Alberto Caorsi, Cristiana Deregibus, Maria C. Bruno, Stefania Amoroso, Antonio Giovarelli, Mirella Porta, Massimo Perin, Paolo Cavallo Tetta, Ciro Camussi, Giovanni Zanone, Maria M. |
| description | Aims/hypothesis
Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes.
Methods
MVs were purified from heterologous human MSCs by differential centrifugation. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with type 1 diabetes at disease onset, and responses to GAD65 stimulation were assessed by IFN-γ enzyme-linked immunosorbent spot analysis. Levels of cytokines and prostaglandin E
2
(PGE
2
) were measured in the supernatant fraction, and T helper 17 (Th17) and regulatory T cell analysis was performed.
Results
MVs were internalised by PBMCs, as assessed by confocal microscopy and flow cytometry analyses. MVs significantly decreased IFN-γ spots and levels in GAD65-stimulated PBMCs, and significantly increased transforming growth factor-β (TGF-β), IL-10, IL-6 and PGE
2
levels. Furthermore, MVs decreased the number of Th17 cells and the levels of IL-17, and increased FoxP3
+
regulatory T cells in GAD65-stimulated PBMCs.
Conclusions/interpretation
These results provide evidence that MSC-derived MVs can inhibit in vitro a proinflammatory response to an islet antigenic stimulus in type 1 diabetes. The action of MVs involves PGE
2
and TGF-β signalling pathways and IL-10 secretion, suggesting a switch to an anti-inflammatory response of T cells. |
| doi_str_mv | 10.1007/s00125-014-3262-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1566858977</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1566858977</sourcerecordid><originalsourceid>FETCH-LOGICAL-c548t-6023425b95d7b3c22a96e737e63603ca459a56257d51d6e8e4801bcf536373d03</originalsourceid><addsrcrecordid>eNqN0c1u1DAQB_AIgehSeAAuyBKqxCXg7zhHVAFFqsSlSNwix57dukqc4HFa9k36uDjs8iEkJE4--Ddjz_yr6jmjrxmlzRuklHFVUyZrwTWv5YNqw6TgNZXcPKw263XNjP5yUj1BvKGUCiX14-qESyOMNnRT3V8so41kBITorvejHQhmGImDYag9pHALnozBpekWMLgBkIyTXwabgVz9UCQBzlNEIHkiAQfIxMYcdhDJbliyLcXEuuCJB2dTP33bD7bgEMlsc4CYkdyFfE3yfgbCiA-2hwz4tHq0tQPCs-N5Wn1-_-7q_KK-_PTh4_nby9opaXKtKReSq75VvumF49y2GhrRgBaaCmelaq3SXDVeMa_BgDSU9W6rhBaN8FScVq8Ofec0fV0AczcGXOeyEaYFO6a0Nsq0TfMftOy-MUUW-vIvejMtKZZBVsWLahUvih1UWS9igm03pzDatO8Y7daEu0PCXUm4WxPuZKl5cey89CP4XxU_Iy3g7AgsOjtsk40u4G9nNJNKrNPwg8NyFXeQ_vjiP1__Du_ovmA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1542278952</pqid></control><display><type>article</type><title>Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Favaro, Enrica ; Carpanetto, Andrea ; Lamorte, Sara ; Fusco, Alberto ; Caorsi, Cristiana ; Deregibus, Maria C. ; Bruno, Stefania ; Amoroso, Antonio ; Giovarelli, Mirella ; Porta, Massimo ; Perin, Paolo Cavallo ; Tetta, Ciro ; Camussi, Giovanni ; Zanone, Maria M.</creator><creatorcontrib>Favaro, Enrica ; Carpanetto, Andrea ; Lamorte, Sara ; Fusco, Alberto ; Caorsi, Cristiana ; Deregibus, Maria C. ; Bruno, Stefania ; Amoroso, Antonio ; Giovarelli, Mirella ; Porta, Massimo ; Perin, Paolo Cavallo ; Tetta, Ciro ; Camussi, Giovanni ; Zanone, Maria M.</creatorcontrib><description>Aims/hypothesis
Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes.
Methods
MVs were purified from heterologous human MSCs by differential centrifugation. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with type 1 diabetes at disease onset, and responses to GAD65 stimulation were assessed by IFN-γ enzyme-linked immunosorbent spot analysis. Levels of cytokines and prostaglandin E
2
(PGE
2
) were measured in the supernatant fraction, and T helper 17 (Th17) and regulatory T cell analysis was performed.
Results
MVs were internalised by PBMCs, as assessed by confocal microscopy and flow cytometry analyses. MVs significantly decreased IFN-γ spots and levels in GAD65-stimulated PBMCs, and significantly increased transforming growth factor-β (TGF-β), IL-10, IL-6 and PGE
2
levels. Furthermore, MVs decreased the number of Th17 cells and the levels of IL-17, and increased FoxP3
+
regulatory T cells in GAD65-stimulated PBMCs.
Conclusions/interpretation
These results provide evidence that MSC-derived MVs can inhibit in vitro a proinflammatory response to an islet antigenic stimulus in type 1 diabetes. The action of MVs involves PGE
2
and TGF-β signalling pathways and IL-10 secretion, suggesting a switch to an anti-inflammatory response of T cells.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-014-3262-4</identifier><identifier>PMID: 24838680</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acids ; Adult ; Antigens ; Biological and medical sciences ; Cell death ; Cytokines - metabolism ; Diabetes ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - metabolism ; Diabetes. Impaired glucose tolerance ; Dinoprostone - metabolism ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Enzymes ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Fibroblasts ; Glutamate Decarboxylase - immunology ; Growth factors ; Human Physiology ; Humans ; Internal Medicine ; Leukocytes ; Lymphocytes ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mesenchymal Stromal Cells - metabolism ; Metabolic Diseases ; MicroRNAs ; Microscopy ; Proteins ; Stem cells ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Young Adult</subject><ispartof>Diabetologia, 2014-08, Vol.57 (8), p.1664-1673</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-6023425b95d7b3c22a96e737e63603ca459a56257d51d6e8e4801bcf536373d03</citedby><cites>FETCH-LOGICAL-c548t-6023425b95d7b3c22a96e737e63603ca459a56257d51d6e8e4801bcf536373d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-014-3262-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-014-3262-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27931,27932,41495,42564,51326</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28614537$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24838680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Favaro, Enrica</creatorcontrib><creatorcontrib>Carpanetto, Andrea</creatorcontrib><creatorcontrib>Lamorte, Sara</creatorcontrib><creatorcontrib>Fusco, Alberto</creatorcontrib><creatorcontrib>Caorsi, Cristiana</creatorcontrib><creatorcontrib>Deregibus, Maria C.</creatorcontrib><creatorcontrib>Bruno, Stefania</creatorcontrib><creatorcontrib>Amoroso, Antonio</creatorcontrib><creatorcontrib>Giovarelli, Mirella</creatorcontrib><creatorcontrib>Porta, Massimo</creatorcontrib><creatorcontrib>Perin, Paolo Cavallo</creatorcontrib><creatorcontrib>Tetta, Ciro</creatorcontrib><creatorcontrib>Camussi, Giovanni</creatorcontrib><creatorcontrib>Zanone, Maria M.</creatorcontrib><title>Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes.
Methods
MVs were purified from heterologous human MSCs by differential centrifugation. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with type 1 diabetes at disease onset, and responses to GAD65 stimulation were assessed by IFN-γ enzyme-linked immunosorbent spot analysis. Levels of cytokines and prostaglandin E
2
(PGE
2
) were measured in the supernatant fraction, and T helper 17 (Th17) and regulatory T cell analysis was performed.
Results
MVs were internalised by PBMCs, as assessed by confocal microscopy and flow cytometry analyses. MVs significantly decreased IFN-γ spots and levels in GAD65-stimulated PBMCs, and significantly increased transforming growth factor-β (TGF-β), IL-10, IL-6 and PGE
2
levels. Furthermore, MVs decreased the number of Th17 cells and the levels of IL-17, and increased FoxP3
+
regulatory T cells in GAD65-stimulated PBMCs.
Conclusions/interpretation
These results provide evidence that MSC-derived MVs can inhibit in vitro a proinflammatory response to an islet antigenic stimulus in type 1 diabetes. The action of MVs involves PGE
2
and TGF-β signalling pathways and IL-10 secretion, suggesting a switch to an anti-inflammatory response of T cells.</description><subject>Acids</subject><subject>Adult</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Cell death</subject><subject>Cytokines - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Dinoprostone - metabolism</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Enzymes</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Glutamate Decarboxylase - immunology</subject><subject>Growth factors</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Leukocytes</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Metabolic Diseases</subject><subject>MicroRNAs</subject><subject>Microscopy</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Young Adult</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqN0c1u1DAQB_AIgehSeAAuyBKqxCXg7zhHVAFFqsSlSNwix57dukqc4HFa9k36uDjs8iEkJE4--Ddjz_yr6jmjrxmlzRuklHFVUyZrwTWv5YNqw6TgNZXcPKw263XNjP5yUj1BvKGUCiX14-qESyOMNnRT3V8so41kBITorvejHQhmGImDYag9pHALnozBpekWMLgBkIyTXwabgVz9UCQBzlNEIHkiAQfIxMYcdhDJbliyLcXEuuCJB2dTP33bD7bgEMlsc4CYkdyFfE3yfgbCiA-2hwz4tHq0tQPCs-N5Wn1-_-7q_KK-_PTh4_nby9opaXKtKReSq75VvumF49y2GhrRgBaaCmelaq3SXDVeMa_BgDSU9W6rhBaN8FScVq8Ofec0fV0AczcGXOeyEaYFO6a0Nsq0TfMftOy-MUUW-vIvejMtKZZBVsWLahUvih1UWS9igm03pzDatO8Y7daEu0PCXUm4WxPuZKl5cey89CP4XxU_Iy3g7AgsOjtsk40u4G9nNJNKrNPwg8NyFXeQ_vjiP1__Du_ovmA</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Favaro, Enrica</creator><creator>Carpanetto, Andrea</creator><creator>Lamorte, Sara</creator><creator>Fusco, Alberto</creator><creator>Caorsi, Cristiana</creator><creator>Deregibus, Maria C.</creator><creator>Bruno, Stefania</creator><creator>Amoroso, Antonio</creator><creator>Giovarelli, Mirella</creator><creator>Porta, Massimo</creator><creator>Perin, Paolo Cavallo</creator><creator>Tetta, Ciro</creator><creator>Camussi, Giovanni</creator><creator>Zanone, Maria M.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20140801</creationdate><title>Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes</title><author>Favaro, Enrica ; Carpanetto, Andrea ; Lamorte, Sara ; Fusco, Alberto ; Caorsi, Cristiana ; Deregibus, Maria C. ; Bruno, Stefania ; Amoroso, Antonio ; Giovarelli, Mirella ; Porta, Massimo ; Perin, Paolo Cavallo ; Tetta, Ciro ; Camussi, Giovanni ; Zanone, Maria M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c548t-6023425b95d7b3c22a96e737e63603ca459a56257d51d6e8e4801bcf536373d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acids</topic><topic>Adult</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Cell death</topic><topic>Cytokines - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Dinoprostone - metabolism</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Enzymes</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Glutamate Decarboxylase - immunology</topic><topic>Growth factors</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Leukocytes</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Metabolic Diseases</topic><topic>MicroRNAs</topic><topic>Microscopy</topic><topic>Proteins</topic><topic>Stem cells</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Favaro, Enrica</creatorcontrib><creatorcontrib>Carpanetto, Andrea</creatorcontrib><creatorcontrib>Lamorte, Sara</creatorcontrib><creatorcontrib>Fusco, Alberto</creatorcontrib><creatorcontrib>Caorsi, Cristiana</creatorcontrib><creatorcontrib>Deregibus, Maria C.</creatorcontrib><creatorcontrib>Bruno, Stefania</creatorcontrib><creatorcontrib>Amoroso, Antonio</creatorcontrib><creatorcontrib>Giovarelli, Mirella</creatorcontrib><creatorcontrib>Porta, Massimo</creatorcontrib><creatorcontrib>Perin, Paolo Cavallo</creatorcontrib><creatorcontrib>Tetta, Ciro</creatorcontrib><creatorcontrib>Camussi, Giovanni</creatorcontrib><creatorcontrib>Zanone, Maria M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Favaro, Enrica</au><au>Carpanetto, Andrea</au><au>Lamorte, Sara</au><au>Fusco, Alberto</au><au>Caorsi, Cristiana</au><au>Deregibus, Maria C.</au><au>Bruno, Stefania</au><au>Amoroso, Antonio</au><au>Giovarelli, Mirella</au><au>Porta, Massimo</au><au>Perin, Paolo Cavallo</au><au>Tetta, Ciro</au><au>Camussi, Giovanni</au><au>Zanone, Maria M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>57</volume><issue>8</issue><spage>1664</spage><epage>1673</epage><pages>1664-1673</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes.
Methods
MVs were purified from heterologous human MSCs by differential centrifugation. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with type 1 diabetes at disease onset, and responses to GAD65 stimulation were assessed by IFN-γ enzyme-linked immunosorbent spot analysis. Levels of cytokines and prostaglandin E
2
(PGE
2
) were measured in the supernatant fraction, and T helper 17 (Th17) and regulatory T cell analysis was performed.
Results
MVs were internalised by PBMCs, as assessed by confocal microscopy and flow cytometry analyses. MVs significantly decreased IFN-γ spots and levels in GAD65-stimulated PBMCs, and significantly increased transforming growth factor-β (TGF-β), IL-10, IL-6 and PGE
2
levels. Furthermore, MVs decreased the number of Th17 cells and the levels of IL-17, and increased FoxP3
+
regulatory T cells in GAD65-stimulated PBMCs.
Conclusions/interpretation
These results provide evidence that MSC-derived MVs can inhibit in vitro a proinflammatory response to an islet antigenic stimulus in type 1 diabetes. The action of MVs involves PGE
2
and TGF-β signalling pathways and IL-10 secretion, suggesting a switch to an anti-inflammatory response of T cells.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24838680</pmid><doi>10.1007/s00125-014-3262-4</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetologia, 2014-08, Vol.57 (8), p.1664-1673 |
| issn | 0012-186X 1432-0428 |
| language | eng |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Acids Adult Antigens Biological and medical sciences Cell death Cytokines - metabolism Diabetes Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - metabolism Diabetes. Impaired glucose tolerance Dinoprostone - metabolism Endocrine pancreas. Apud cells (diseases) Endocrinopathies Enzymes Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Fibroblasts Glutamate Decarboxylase - immunology Growth factors Human Physiology Humans Internal Medicine Leukocytes Lymphocytes Male Medical sciences Medicine Medicine & Public Health Mesenchymal Stromal Cells - metabolism Metabolic Diseases MicroRNAs Microscopy Proteins Stem cells T-Lymphocytes - immunology T-Lymphocytes - metabolism Young Adult |
| title | Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes |
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