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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function</title><author><name sortKey="Gousopoulos, Epameinondas" sort="Gousopoulos, Epameinondas" uniqKey="Gousopoulos E" first="Epameinondas" last="Gousopoulos">Epameinondas Gousopoulos</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Bachmann, Samia B" sort="Bachmann, Samia B" uniqKey="Bachmann S" first="Samia B." last="Bachmann">Samia B. Bachmann</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Scholl, Jeannette" sort="Scholl, Jeannette" uniqKey="Scholl J" first="Jeannette" last="Scholl">Jeannette Scholl</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dionyssiou, Dimitris" sort="Dionyssiou, Dimitris" uniqKey="Dionyssiou D" first="Dimitris" last="Dionyssiou">Dimitris Dionyssiou</name><affiliation><nlm:aff id="A2">Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.</nlm:aff></affiliation></author><author><name sortKey="Demiri, Efterpi" sort="Demiri, Efterpi" uniqKey="Demiri E" first="Efterpi" last="Demiri">Efterpi Demiri</name><affiliation><nlm:aff id="A2">Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.</nlm:aff></affiliation></author><author><name sortKey="Halin, Cornelia" sort="Halin, Cornelia" uniqKey="Halin C" first="Cornelia" last="Halin">Cornelia Halin</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dieterich, Lothar C" sort="Dieterich, Lothar C" uniqKey="Dieterich L" first="Lothar C." last="Dieterich">Lothar C. Dieterich</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27734032</idno><idno type="pmc">5054740</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054740</idno><idno type="RBID">PMC:5054740</idno><idno type="doi">10.1172/jci.insight.89081</idno><date when="????">????</date><idno type="wicri:Area/Pmc/Corpus">003009</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003009</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function</title><author><name sortKey="Gousopoulos, Epameinondas" sort="Gousopoulos, Epameinondas" uniqKey="Gousopoulos E" first="Epameinondas" last="Gousopoulos">Epameinondas Gousopoulos</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Bachmann, Samia B" sort="Bachmann, Samia B" uniqKey="Bachmann S" first="Samia B." last="Bachmann">Samia B. Bachmann</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Scholl, Jeannette" sort="Scholl, Jeannette" uniqKey="Scholl J" first="Jeannette" last="Scholl">Jeannette Scholl</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dionyssiou, Dimitris" sort="Dionyssiou, Dimitris" uniqKey="Dionyssiou D" first="Dimitris" last="Dionyssiou">Dimitris Dionyssiou</name><affiliation><nlm:aff id="A2">Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.</nlm:aff></affiliation></author><author><name sortKey="Demiri, Efterpi" sort="Demiri, Efterpi" uniqKey="Demiri E" first="Efterpi" last="Demiri">Efterpi Demiri</name><affiliation><nlm:aff id="A2">Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.</nlm:aff></affiliation></author><author><name sortKey="Halin, Cornelia" sort="Halin, Cornelia" uniqKey="Halin C" first="Cornelia" last="Halin">Cornelia Halin</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dieterich, Lothar C" sort="Dieterich, Lothar C" uniqKey="Dieterich L" first="Lothar C." last="Dieterich">Lothar C. Dieterich</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation><nlm:aff id="A1">Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</nlm:aff></affiliation></author></analytic><series><title level="j">JCI Insight</title><idno type="eISSN">2379-3708</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell–related networks, and indeed depletion of CD4<sup>+</sup> cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema. Indeed, increased infiltration of Tregs was identified in mouse lymphedematous skin and in human lymphedema specimens. To investigate the role of Tregs during disease progression, loss-of-function and gain-of-function studies were performed. Depletion of Tregs in transgenic mice with Tregs expressing the primate diphtheria toxin receptor and green fluorescent protein (<italic>Foxp3</italic>-DTR-GFP) mice led to exacerbated edema, concomitant with increased infiltration of immune cells and a mixed T<sub>H</sub>1/T<sub>H</sub>2 cytokine profile. Conversely, expansion of Tregs using IL-2/anti–IL-2 mAb complexes significantly reduced lymphedema development. Therapeutic application of adoptively transferred Tregs upon lymphedema establishment reversed all of the major hallmarks of lymphedema, including edema, inflammation, and fibrosis, and also promoted lymphatic drainage function. Collectively, our results reveal that Treg application constitutes a potential new curative treatment modality for lymphedema.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">JCI Insight</journal-id><journal-id journal-id-type="iso-abbrev">JCI Insight</journal-id><journal-id journal-id-type="publisher-id">JCI Insight</journal-id><journal-title-group><journal-title>JCI Insight</journal-title></journal-title-group><issn pub-type="epub">2379-3708</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27734032</article-id><article-id pub-id-type="pmc">5054740</article-id><article-id pub-id-type="publisher-id">89081</article-id><article-id pub-id-type="doi">10.1172/jci.insight.89081</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gousopoulos</surname><given-names>Epameinondas</given-names></name><email>e.gousopoulos@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Proulx</surname><given-names>Steven T.</given-names></name><email>steven.proulx@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bachmann</surname><given-names>Samia B.</given-names></name><email>samia.bachmann@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Scholl</surname><given-names>Jeannette</given-names></name><email>jeannette.scholl@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dionyssiou</surname><given-names>Dimitris</given-names></name><email>diodi@auth.gr</email><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Demiri</surname><given-names>Efterpi</given-names></name><email>demirie@auth.gr</email><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Halin</surname><given-names>Cornelia</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dieterich</surname><given-names>Lothar C.</given-names></name><email>Lothar.dieterich@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Detmar</surname><given-names>Michael</given-names></name><email>michael.detmar@pharma.ethz.ch</email><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.</aff><aff id="A2"><label>2</label>Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece.</aff><author-notes><corresp>Address correspondence to: Michael Detmar, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir-Prelog-Weg 3, HCI H303, CH-8093 Zurich, Switzerland. Phone: 41.44.633.7361; E-mail: <email>michael.detmar@pharma.ethz.ch</email>.</corresp></author-notes><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2016-10-06"><day>6</day><month>10</month><year>2016</year></pub-date><pub-date date-type="collection" publication-format="electronic" iso-8601-date="2016-10-06"><day>6</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>6</day><month>10</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and
0 days and was based on the
<volume>1</volume><issue>16</issue><elocation-id>e89081</elocation-id><history><date date-type="received"><day>13</day><month>6</month><year>2016</year></date><date date-type="accepted"><day>6</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, American Society for Clinical Investigation</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>American Society for Clinical Investigation</copyright-holder></permissions><self-uri xlink:href="https://insight.jci.org/articles/view/89081">This article is available online at https://insight.jci.org/articles/view/89081</self-uri><abstract><p>Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell–related networks, and indeed depletion of CD4<sup>+</sup> cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema. Indeed, increased infiltration of Tregs was identified in mouse lymphedematous skin and in human lymphedema specimens. To investigate the role of Tregs during disease progression, loss-of-function and gain-of-function studies were performed. Depletion of Tregs in transgenic mice with Tregs expressing the primate diphtheria toxin receptor and green fluorescent protein (<italic>Foxp3</italic>-DTR-GFP) mice led to exacerbated edema, concomitant with increased infiltration of immune cells and a mixed T<sub>H</sub>1/T<sub>H</sub>2 cytokine profile. Conversely, expansion of Tregs using IL-2/anti–IL-2 mAb complexes significantly reduced lymphedema development. Therapeutic application of adoptively transferred Tregs upon lymphedema establishment reversed all of the major hallmarks of lymphedema, including edema, inflammation, and fibrosis, and also promoted lymphatic drainage function. Collectively, our results reveal that Treg application constitutes a potential new curative treatment modality for lymphedema.</p></abstract><abstract abstract-type="toc"><p>Regulatory T cells modulate lymphedema development, and therapeutic transfer of regulatory T cells ameliorates lymphedema by diminishing inflammation, fibrosis, and improving lymphatic vessel function.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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