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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EAllogeneic hematopoietic stem-cell transplantation is a promising treatment approach in patients who require hematopoietic stem cell transplantation. A significant drawback is the occurrence of acute graft-vs-host disease, which occurs when newly transplanted donor lymphocytes attack the transplant recipient\u0027s body. The discovery of the Th17-prone CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E T-cell population may be an early biomarker for intestinal graft-vs-host disease leading to more specific preventions strategies.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eacute graft-vs-host disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eallogeneic hematopoietic stem-cell transplantation\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eearly quantification\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ebiomarker\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egastrointestinal\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EAcute graft-vs-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), primarily affecting the skin, liver, and gastrointestinal (GI) tract. GVHD limits the role of transplantation in other clinical settings, such as the treatment of severe autoimmune disorders. T lymphocytes in the peripheral blood play a central role in immunity and in the process whereby newly transplanted donor cells attack the transplant recipient\u2019s body.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn a late-breaking clinical trial [Li W et al. \u003Cem\u003EBlood.\u003C\/em\u003E 2014], Wei Li, MD, PhD, Indiana University, Indianapolis, Indiana, USA, reported that early quantification of a novel Th17-prone CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E inducible T-cell costimulator (ICOS)\u2013induced population may identify patients at risk for GI GVHD development and subsequent mortality.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPeripheral blood cells from 214 HSCT patients (71 GI GVHD, 48 no GVHD, 33 non-GVHD enteritis, 22 skin-first GVHD, 40 isolated-skin GVHD) were analyzed using proteomics 14 days prior to the onset of GVHD symptoms. Biomarkers that increased 1.5-fold were identified in the plasma from GI GVHD patients and compared with HSCT patients without GVHD at matched time points. Two proteins were identified: CD146, a cell adhesion and trafficking molecule expressed on a subset of CD4\u003Csup\u003E+\u003C\/sup\u003E T cells and endothelial cells, and the chemokine (C-C motif) ligand 14, which binds to the chemokine receptor CCR5 on T cells.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ECD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E T-cell frequency was significantly increased in patients with GI GVD compared with patients without GVHD (\u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.0001), non-GVHD enteritis (\u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.0001), or isolated-skin GVHD (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.007) but not with skin-first and then GI GVHD (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.28).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E T cells were not correlated with GI histologic severity and increased prior to GVHD clinical onset. CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E T cells were Th17 prone in that Th17 cells express more CD146 than Th1 cells. The activation marker ICOS, known to be critical for the development of human Th17 cells, was also critical for the expression of CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E on T cells.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ETh17 cells migrated more efficiently through endothelial-cell monolayers than their Th1 counterparts, suggesting that endothelium may play an important role in recruiting pathogenic T cells. This was supported by evidence showing that CD146 Th17 transmigration is reduced by CD146 shRNA knockdown on T cells. However, knockdown of CD146 on endothelial cells does not reduce T-cell transmigration.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EFinally, to evaluate the in vivo function of CD146 T cells, donor human T cells knockdown with CD146shRNA were transmigrated into a xenogeneic GVHD mouse model. Mice did not lose weight, had similar human T-cell engraftment (hCD4), had fewer splenic CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003ET cells, and expressed less interferon gamma 53 days after transplant, providing proof that CD146 promotes infiltration of pathogenic T cells into GVHD target organs.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe CD146\u003Csup\u003E+\u003C\/sup\u003ECCR5\u003Csup\u003E+\u003C\/sup\u003E cell population is a biomarker of GI GVHD. Early quantification of this population of cells may predict the development of GI GVHD and offer more specific prevention and therapeutic strategies, thereby reducing mortality.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/55\/8.1.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzo9aq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}