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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An activated Th17-prone T cell subset involved in chronic graft-versus<italic>-</italic>host disease sensitive to pharmacological inhibition</title><author><name sortKey="Forcade, Edouard" sort="Forcade, Edouard" uniqKey="Forcade E" first="Edouard" last="Forcade">Edouard Forcade</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Hematology and Cell Therapy, University Hospital, Bordeaux, France.</nlm:aff></affiliation></author><author><name sortKey="Paz, Katelyn" sort="Paz, Katelyn" uniqKey="Paz K" first="Katelyn" last="Paz">Katelyn Paz</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Flynn, Ryan" sort="Flynn, Ryan" uniqKey="Flynn R" first="Ryan" last="Flynn">Ryan Flynn</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Griesenauer, Brad" sort="Griesenauer, Brad" uniqKey="Griesenauer B" first="Brad" last="Griesenauer">Brad Griesenauer</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Amet, Tohti" sort="Amet, Tohti" uniqKey="Amet T" first="Tohti" last="Amet">Tohti Amet</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Liu, Liangyi" sort="Liu, Liangyi" uniqKey="Liu L" first="Liangyi" last="Liu">Liangyi Liu</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Bakoyannis, Giorgos" sort="Bakoyannis, Giorgos" uniqKey="Bakoyannis G" first="Giorgos" last="Bakoyannis">Giorgos Bakoyannis</name><affiliation><nlm:aff id="A10">Department of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Jiang, Di" sort="Jiang, Di" uniqKey="Jiang D" first="Di" last="Jiang">Di Jiang</name><affiliation><nlm:aff id="A11">National Jewish Health, Denver, Colorado, USA.</nlm:aff></affiliation></author><author><name sortKey="Chu, Hong Wei" sort="Chu, Hong Wei" uniqKey="Chu H" first="Hong Wei" last="Chu">Hong Wei Chu</name><affiliation><nlm:aff id="A11">National Jewish Health, Denver, Colorado, USA.</nlm:aff></affiliation></author><author><name sortKey="Lobera, Mercedes" sort="Lobera, Mercedes" uniqKey="Lobera M" first="Mercedes" last="Lobera">Mercedes Lobera</name><affiliation><nlm:aff id="A12">GlaxoSmithKline, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Yang, Jianfei" sort="Yang, Jianfei" uniqKey="Yang J" first="Jianfei" last="Yang">Jianfei Yang</name><affiliation><nlm:aff id="A12">GlaxoSmithKline, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Wilkes, David S" sort="Wilkes, David S" uniqKey="Wilkes D" first="David S." last="Wilkes">David S. Wilkes</name><affiliation><nlm:aff id="A13">Dean, University of Virginia, School of Medicine, Charlottesville, Virginia, USA.</nlm:aff></affiliation></author><author><name sortKey="Du, Jing" sort="Du, Jing" uniqKey="Du J" first="Jing" last="Du">Jing Du</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Gartlan, Kate" sort="Gartlan, Kate" uniqKey="Gartlan K" first="Kate" last="Gartlan">Kate Gartlan</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hill, Geoffrey R" sort="Hill, Geoffrey R" uniqKey="Hill G" first="Geoffrey R." last="Hill">Geoffrey R. Hill</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Macdonald, Kelli P A" sort="Macdonald, Kelli P A" uniqKey="Macdonald K" first="Kelli P. A." last="Macdonald">Kelli P. A. Macdonald</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Espada, Eduardo L" sort="Espada, Eduardo L" uniqKey="Espada E" first="Eduardo L." last="Espada">Eduardo L. Espada</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Blanco, Patrick" sort="Blanco, Patrick" uniqKey="Blanco P" first="Patrick" last="Blanco">Patrick Blanco</name><affiliation><nlm:aff id="A3">Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.</nlm:aff></affiliation></author><author><name sortKey="Serody, Jonathan S" sort="Serody, Jonathan S" uniqKey="Serody J" first="Jonathan S." last="Serody">Jonathan S. Serody</name><affiliation><nlm:aff id="A15">Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Koreth, John" sort="Koreth, John" uniqKey="Koreth J" first="John" last="Koreth">John Koreth</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Cutler, Corey S" sort="Cutler, Corey S" uniqKey="Cutler C" first="Corey S." last="Cutler">Corey S. Cutler</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Antin, Joseph H" sort="Antin, Joseph H" uniqKey="Antin J" first="Joseph H." last="Antin">Joseph H. Antin</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Soiffer, Robert J" sort="Soiffer, Robert J" uniqKey="Soiffer R" first="Robert J." last="Soiffer">Robert J. Soiffer</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Ritz, Jerome" sort="Ritz, Jerome" uniqKey="Ritz J" first="Jerome" last="Ritz">Jerome Ritz</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Paczesny, Sophie" sort="Paczesny, Sophie" uniqKey="Paczesny S" first="Sophie" last="Paczesny">Sophie Paczesny</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Blazar, Bruce R" sort="Blazar, Bruce R" uniqKey="Blazar B" first="Bruce R." last="Blazar">Bruce R. Blazar</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28614794</idno><idno type="pmc">5470889</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470889</idno><idno type="RBID">PMC:5470889</idno><idno type="doi">10.1172/jci.insight.92111</idno><date when="????">????</date><idno type="wicri:Area/Pmc/Corpus">001A20</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001A20</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An activated Th17-prone T cell subset involved in chronic graft-versus<italic>-</italic>host disease sensitive to pharmacological inhibition</title><author><name sortKey="Forcade, Edouard" sort="Forcade, Edouard" uniqKey="Forcade E" first="Edouard" last="Forcade">Edouard Forcade</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Hematology and Cell Therapy, University Hospital, Bordeaux, France.</nlm:aff></affiliation></author><author><name sortKey="Paz, Katelyn" sort="Paz, Katelyn" uniqKey="Paz K" first="Katelyn" last="Paz">Katelyn Paz</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Flynn, Ryan" sort="Flynn, Ryan" uniqKey="Flynn R" first="Ryan" last="Flynn">Ryan Flynn</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Griesenauer, Brad" sort="Griesenauer, Brad" uniqKey="Griesenauer B" first="Brad" last="Griesenauer">Brad Griesenauer</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Amet, Tohti" sort="Amet, Tohti" uniqKey="Amet T" first="Tohti" last="Amet">Tohti Amet</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Liu, Liangyi" sort="Liu, Liangyi" uniqKey="Liu L" first="Liangyi" last="Liu">Liangyi Liu</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Bakoyannis, Giorgos" sort="Bakoyannis, Giorgos" uniqKey="Bakoyannis G" first="Giorgos" last="Bakoyannis">Giorgos Bakoyannis</name><affiliation><nlm:aff id="A10">Department of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Jiang, Di" sort="Jiang, Di" uniqKey="Jiang D" first="Di" last="Jiang">Di Jiang</name><affiliation><nlm:aff id="A11">National Jewish Health, Denver, Colorado, USA.</nlm:aff></affiliation></author><author><name sortKey="Chu, Hong Wei" sort="Chu, Hong Wei" uniqKey="Chu H" first="Hong Wei" last="Chu">Hong Wei Chu</name><affiliation><nlm:aff id="A11">National Jewish Health, Denver, Colorado, USA.</nlm:aff></affiliation></author><author><name sortKey="Lobera, Mercedes" sort="Lobera, Mercedes" uniqKey="Lobera M" first="Mercedes" last="Lobera">Mercedes Lobera</name><affiliation><nlm:aff id="A12">GlaxoSmithKline, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Yang, Jianfei" sort="Yang, Jianfei" uniqKey="Yang J" first="Jianfei" last="Yang">Jianfei Yang</name><affiliation><nlm:aff id="A12">GlaxoSmithKline, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Wilkes, David S" sort="Wilkes, David S" uniqKey="Wilkes D" first="David S." last="Wilkes">David S. Wilkes</name><affiliation><nlm:aff id="A13">Dean, University of Virginia, School of Medicine, Charlottesville, Virginia, USA.</nlm:aff></affiliation></author><author><name sortKey="Du, Jing" sort="Du, Jing" uniqKey="Du J" first="Jing" last="Du">Jing Du</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Gartlan, Kate" sort="Gartlan, Kate" uniqKey="Gartlan K" first="Kate" last="Gartlan">Kate Gartlan</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hill, Geoffrey R" sort="Hill, Geoffrey R" uniqKey="Hill G" first="Geoffrey R." last="Hill">Geoffrey R. Hill</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Macdonald, Kelli P A" sort="Macdonald, Kelli P A" uniqKey="Macdonald K" first="Kelli P. A." last="Macdonald">Kelli P. A. Macdonald</name><affiliation><nlm:aff id="A14">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:aff></affiliation></author><author><name sortKey="Espada, Eduardo L" sort="Espada, Eduardo L" uniqKey="Espada E" first="Eduardo L." last="Espada">Eduardo L. Espada</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Blanco, Patrick" sort="Blanco, Patrick" uniqKey="Blanco P" first="Patrick" last="Blanco">Patrick Blanco</name><affiliation><nlm:aff id="A3">Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.</nlm:aff></affiliation></author><author><name sortKey="Serody, Jonathan S" sort="Serody, Jonathan S" uniqKey="Serody J" first="Jonathan S." last="Serody">Jonathan S. Serody</name><affiliation><nlm:aff id="A15">Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Koreth, John" sort="Koreth, John" uniqKey="Koreth J" first="John" last="Koreth">John Koreth</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Cutler, Corey S" sort="Cutler, Corey S" uniqKey="Cutler C" first="Corey S." last="Cutler">Corey S. Cutler</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Antin, Joseph H" sort="Antin, Joseph H" uniqKey="Antin J" first="Joseph H." last="Antin">Joseph H. Antin</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Soiffer, Robert J" sort="Soiffer, Robert J" uniqKey="Soiffer R" first="Robert J." last="Soiffer">Robert J. Soiffer</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Ritz, Jerome" sort="Ritz, Jerome" uniqKey="Ritz J" first="Jerome" last="Ritz">Jerome Ritz</name><affiliation><nlm:aff id="A1">Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Paczesny, Sophie" sort="Paczesny, Sophie" uniqKey="Paczesny S" first="Sophie" last="Paczesny">Sophie Paczesny</name><affiliation><nlm:aff id="A6">Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Herman B. Wells Center for Pediatric Research,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="A8">Department of Microbiology and Immunology</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:aff></affiliation></author><author><name sortKey="Blazar, Bruce R" sort="Blazar, Bruce R" uniqKey="Blazar B" first="Bruce R." last="Blazar">Bruce R. Blazar</name><affiliation><nlm:aff id="A5">Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</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>Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic stem cell transplantation requiring novel therapies. CD146 and CCR5 are expressed by activated T cells and associated with increased T cell migration capacity and Th17 polarization. We performed a multiparametric flow cytometry analysis in a cohort of 40 HSCT patients together with a cGvHD murine model to understand the role of CD146-expressing subsets. We observed an increased frequency of CD146<sup>+</sup> CD4 T cells in the 20 patients with active cGvHD with enhanced RORγt expression. This Th17-prone subset was enriched for cells coexpressing CD146 and CCR5 that harbor mixed Th1/Th17 features and were more frequent in cGvHD patients. Utilizing a murine cGvHD model with bronchiolitis obliterans (BO), we observed that donor T cells from CD146-deficient mice versus those from WT mice caused significantly reduced pulmonary cGvHD. Reduced cGvHD was not the result of failed germinal center B cell or T follicular helper cell generation. Instead, CD146-deficient T cells had significantly lower pulmonary macrophage infiltration and T cell CCR5, IL-17, and IFN-γ coexpression, suggesting defective pulmonary end-organ effector mechanisms. We, thus, evaluated the effect of TMP778, a small-molecule RORγt activity inhibitor. TMP778 markedly alleviated cGvHD in murine models similarly to agents targeting the Th17 pathway, such as STAT3 inhibitor or IL-17–blocking antibody. Our data suggest CD146-expressing T cells as a cGvHD biomarker and suggest that targeting the Th17 pathway may represent a promising therapy for cGvHD.</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">28614794</article-id><article-id pub-id-type="pmc">5470889</article-id><article-id pub-id-type="publisher-id">92111</article-id><article-id pub-id-type="doi">10.1172/jci.insight.92111</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>An activated Th17-prone T cell subset involved in chronic graft-versus<italic>-</italic>host disease sensitive to pharmacological inhibition</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Forcade</surname><given-names>Edouard</given-names></name><email>edouardforcade@yahoo.fr</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Paz</surname><given-names>Katelyn</given-names></name><email>good0546@umn.edu</email><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Flynn</surname><given-names>Ryan</given-names></name><email>rflynn85@gmail.com</email><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-4564-7484</contrib-id><name><surname>Griesenauer</surname><given-names>Brad</given-names></name><email>bgriesen@iupui.edu</email><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Amet</surname><given-names>Tohti</given-names></name><email>tamet@iupui.edu</email><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Wei</given-names></name><email>wl1@iupui.edu</email><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Liangyi</given-names></name><email>liangyi.liu@yahoo.com</email><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Bakoyannis</surname><given-names>Giorgos</given-names></name><email>gbakogia@iu.edu</email><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Di</given-names></name><email>JiangD@njhealth.org</email><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Chu</surname><given-names>Hong Wei</given-names></name><email>chuhw@njhealth.org</email><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-0803-1285</contrib-id><name><surname>Lobera</surname><given-names>Mercedes</given-names></name><email>Mercedes.x.lobera@gsk.com</email><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Jianfei</given-names></name><email>jianfei.x.yang@gsk.com</email><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Wilkes</surname><given-names>David S.</given-names></name><email>Dsw4n@virginia.edu</email><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Du</surname><given-names>Jing</given-names></name><email>duxxx209@umn.edu</email><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Gartlan</surname><given-names>Kate</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Hill</surname><given-names>Geoffrey R.</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>MacDonald</surname><given-names>Kelli P.A.</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Espada</surname><given-names>Eduardo L.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Blanco</surname><given-names>Patrick</given-names></name><email>patrick.blanco@chu-bordeaux.fr</email><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-4568-1092</contrib-id><name><surname>Serody</surname><given-names>Jonathan S.</given-names></name><email>jonathan_serody@med.unc.edu</email><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Koreth</surname><given-names>John</given-names></name><email>john_koreth@dfci.harvard.edu</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cutler</surname><given-names>Corey S.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-4627-1714</contrib-id><name><surname>Antin</surname><given-names>Joseph H.</given-names></name><email>jantin@partners.org</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Soiffer</surname><given-names>Robert J.</given-names></name><email>robert_soiffer@dfci.harvard.edu</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5526-4669</contrib-id><name><surname>Ritz</surname><given-names>Jerome</given-names></name><email>jerome_ritz@dfci.harvard.edu</email><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5571-2775</contrib-id><name><surname>Paczesny</surname><given-names>Sophie</given-names></name><email>sophpacz@iu.edu</email><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Blazar</surname><given-names>Bruce R.</given-names></name><email>blaza001@umn.edu</email><xref ref-type="aff" rid="A5">5</xref></contrib></contrib-group><aff id="A1"><label>1</label>Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.</aff><aff id="A2"><label>2</label>Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A3"><label>3</label>Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.</aff><aff id="A4"><label>4</label>Department of Hematology and Cell Therapy, University Hospital, Bordeaux, France.</aff><aff id="A5"><label>5</label>Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.</aff><aff id="A6"><label>6</label>Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</aff><aff id="A7"><label>7</label>Herman B. Wells Center for Pediatric Research,</aff><aff id="A8"><label>8</label>Department of Microbiology and Immunology, and</aff><aff id="A9"><label>9</label>Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.</aff><aff id="A10"><label>10</label>Department of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indiana, USA.</aff><aff id="A11"><label>11</label>National Jewish Health, Denver, Colorado, USA.</aff><aff id="A12"><label>12</label>GlaxoSmithKline, Cambridge, Massachusetts, USA.</aff><aff id="A13"><label>13</label>Dean, University of Virginia, School of Medicine, Charlottesville, Virginia, USA.</aff><aff id="A14"><label>14</label>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</aff><aff id="A15"><label>15</label>Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</aff><author-notes><corresp>Address correspondence to: Bruce R. Blazar, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, 420 Delaware Strett SE, MMC 109, Minneapolis, Minnesota 55455, USA. Phone: 612.626.2734; Email: <email>blaza001@umn.edu</email>. Or to: Sophie Paczesny, Indiana University School of Medicine, 1044 W. Walnut Street, Room R4-425, Indianapolis, Indiana 46202, USA. Phone: 317.278.5487; Email: <email>sophpacz@iu.edu</email>.</corresp><fn><p><bold>Authorship note:</bold> EF, KP, and RF contributed equally as first authors. JR, SP, and BRB contributed equally as senior authors.</p></fn></author-notes><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2017-06-15T09:00:00-0400"><day>15</day><month>6</month><year>2017</year></pub-date><pub-date date-type="collection" publication-format="electronic" iso-8601-date="2017-06-15T09:00:00-0400"><day>15</day><month>6</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>6</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 0 months and
0 days and was based on the
<volume>2</volume><issue>12</issue><elocation-id>e92111</elocation-id><history><date date-type="received"><day>9</day><month>12</month><year>2016</year></date><date date-type="accepted"><day>16</day><month>5</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017, American Society for Clinical Investigation</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>American Society for Clinical Investigation</copyright-holder></permissions><self-uri xlink:href="https://insight.jci.org/articles/view/92111">This article is available online at https://insight.jci.org/articles/view/92111</self-uri><abstract><p>Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic stem cell transplantation requiring novel therapies. CD146 and CCR5 are expressed by activated T cells and associated with increased T cell migration capacity and Th17 polarization. We performed a multiparametric flow cytometry analysis in a cohort of 40 HSCT patients together with a cGvHD murine model to understand the role of CD146-expressing subsets. We observed an increased frequency of CD146<sup>+</sup> CD4 T cells in the 20 patients with active cGvHD with enhanced RORγt expression. This Th17-prone subset was enriched for cells coexpressing CD146 and CCR5 that harbor mixed Th1/Th17 features and were more frequent in cGvHD patients. Utilizing a murine cGvHD model with bronchiolitis obliterans (BO), we observed that donor T cells from CD146-deficient mice versus those from WT mice caused significantly reduced pulmonary cGvHD. Reduced cGvHD was not the result of failed germinal center B cell or T follicular helper cell generation. Instead, CD146-deficient T cells had significantly lower pulmonary macrophage infiltration and T cell CCR5, IL-17, and IFN-γ coexpression, suggesting defective pulmonary end-organ effector mechanisms. We, thus, evaluated the effect of TMP778, a small-molecule RORγt activity inhibitor. TMP778 markedly alleviated cGvHD in murine models similarly to agents targeting the Th17 pathway, such as STAT3 inhibitor or IL-17–blocking antibody. Our data suggest CD146-expressing T cells as a cGvHD biomarker and suggest that targeting the Th17 pathway may represent a promising therapy for cGvHD.</p></abstract><abstract abstract-type="toc"><p>CD146-expressing cells represent a pathogenic subset with a Th17 profile that are involved in chronic GVHD and can be targeted by a small molecule RORγt inhibitor.</p></abstract><kwd-group kwd-group-type="specialties"><kwd>Immunology</kwd><kwd>Transplantation</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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