{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:55:23Z","timestamp":1782924923510,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T00:00:00Z","timestamp":1470873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Next-Generation BioGreen 21 Program","award":["PJ 00965302"],"award-info":[{"award-number":["PJ 00965302"]}]},{"name":"Cooperative Research Program for Agriculture Science & Technology Development","award":["PJ01094404"],"award-info":[{"award-number":["PJ01094404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system\u2010related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double \u03b1\u20101,3\u2010galactosyltransferase (GalT) knockout (KO) pigs (&lt;6 weeks old). The immunosuppressive regimen included administration of cobra venom factor, anti\u2010thymocyte globulin, rituximab, and anti\u2010CD154 monoclonal antibodies to recipients before and after grafting. Islets were xenografted into the portal vein in type 1 diabetic monkeys, and the heart was xenografted by heterotopic abdominal heart transplantation. Genes from recipient blood were analyzed using RT<jats:sup>2<\/jats:sup> profiler PCR arrays and the web\u2010based RT<jats:sup>2<\/jats:sup> profiler PCR array software v.3.5. Recipients treated with immunosuppressive agents without grafting showed significant downregulation of <jats:italic>CCL5<\/jats:italic>,<jats:italic> CCR4<\/jats:italic>,<jats:italic> CCR6<\/jats:italic>,<jats:italic> CD4<\/jats:italic>,<jats:italic> CD40LG<\/jats:italic>,<jats:italic> CXCR3<\/jats:italic>,<jats:italic> FASLG<\/jats:italic>,<jats:italic> CXCR3<\/jats:italic>,<jats:italic> FOXP3<\/jats:italic>,<jats:italic> GATA3<\/jats:italic>,<jats:italic> IGNG<\/jats:italic>,<jats:italic> L10<\/jats:italic>,<jats:italic> IL23A<\/jats:italic>,<jats:italic> TRAF6<\/jats:italic>,<jats:italic> MAPK8<\/jats:italic>,<jats:italic> MIF<\/jats:italic>,<jats:italic> STAT4<\/jats:italic>,<jats:italic> TBX21<\/jats:italic>,<jats:italic> TLR3<\/jats:italic>,<jats:italic> TLR7<\/jats:italic>, and <jats:italic>TYK2<\/jats:italic> and upregulation of <jats:italic>IFNGR1<\/jats:italic>; thus, genes involved in protection against viral and bacterial infection were downregulated, confirming the risk of infection. Notably, C3\u2010level control resulted in xenograft failure within 2 days because of a 7\u2010 to 11\u2010fold increase in all xenotransplanted models. Islet grafting using single GalT\u2010KO pigs resulted in upregulation of <jats:italic>CXCL10<\/jats:italic> and <jats:italic>MX1<\/jats:italic>, early inflammation, and acute rejection\u2010associated signals at 2 days after xenografting. We observed at least 5\u2010fold upregulation in recipients transplanted with islets grafts from single (<jats:italic>MX1<\/jats:italic>) or double (<jats:italic>C3<\/jats:italic>,<jats:italic> CCR8<\/jats:italic>,<jats:italic> IL6<\/jats:italic>,<jats:italic> IL13<\/jats:italic>,<jats:italic> IRF6<\/jats:italic>,<jats:italic> CXCL10<\/jats:italic>, and <jats:italic>MX1<\/jats:italic>) GalT\u2010KO pigs after 77 days; single GalT\u2010KO incurred early losses owing to immune attacks. Our results suggest that this novel, simple, non\u2010invasive, and time\u2010efficient procedure (requiring only 1.5 ml blood) for evaluating graft success, minimizing immune rejection, and blocking infection.<\/jats:p>","DOI":"10.1111\/xen.12249","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T06:36:53Z","timestamp":1470897413000},"page":"357-369","source":"Crossref","is-referenced-by-count":9,"title":["Molecular immunology profiles of monkeys following xenografting with the islets and heart of \u03b1\u20101,3\u2010galactosyltransferase knockout pigs"],"prefix":"10.1111","volume":"23","author":[{"given":"Sun A","family":"Ock","sequence":"first","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungkyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keon Bong","family":"Oh","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongsoo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ik Jin","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Surgery Konkuk University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curie","family":"Ahn","sequence":"additional","affiliation":[{"name":"Transplantation Center Seoul National University Hospital Seoul Korea"},{"name":"Designed Animal &amp; Transplantation Research Institute Institute of Green BioScience &amp; Technology Seoul National University Pyeongchang Gangwon\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Keun","family":"Chee","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Konkuk University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwajung","family":"Kim","sequence":"additional","affiliation":[{"name":"Transplantation Center Seoul National University Hospital Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Berm","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngim","family":"Kim","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi\u2010Sun","family":"Im","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Division National Institute of Animal Science Rural Development Administration Wanju\u2010gun Jeollabuk\u2010do Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EungWoo","family":"Park","sequence":"additional","affiliation":[{"name":"Animal 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