{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:44:14Z","timestamp":1791096254395,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant immunosuppressive drugs incompletely control GVHD and increase susceptibility to opportunistic infections. In this study, we used flagellin, a TLR5 agonist protein (\u223c50 kDa) extracted from bacterial flagella, as a novel experimental treatment strategy to reduce both acute and chronic GVHD in allogeneic HSCT recipients. On the basis of the radioprotective effects of flagellin, we hypothesized that flagellin could ameliorate GVHD in lethally irradiated murine models of allogeneic HSCT. Two doses of highly purified flagellin (administered 3 h before irradiation and 24 h after HSCT) reduced GVHD and led to better survival in both H-2b \u2192 CB6F1 and H-2K \u2192 B6 allogeneic HSCT models while preserving &amp;gt;99% donor T cell chimerism. Flagellin treatment preserved long-term posttransplant immune reconstitution characterized by more donor thymic-derived CD4+CD25+Foxp3+ regulatory T cells and significantly enhanced antiviral immunity after murine CMV infection. The proliferation index and activation status of donor spleen-derived T cells and serum concentration of proinflammatory cytokines in flagellin-treated recipients were reduced significantly within 4 d posttransplant compared with those of the PBS-treated control recipients. Allogeneic transplantation of radiation chimeras previously engrafted with TLR5 knockout hematopoietic cells showed that interactions between flagellin and TLR5 expressed on both donor hematopoietic and host nonhematopoietic cells were required to reduce GVHD. Thus, the peritransplant administration of flagellin is a novel therapeutic approach to control GVHD while preserving posttransplant donor immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1101334","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T05:50:52Z","timestamp":1318917052000},"page":"5130-5140","source":"Crossref","is-referenced-by-count":52,"title":["Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity"],"prefix":"10.1093","volume":"187","author":[{"given":"Mohammad S","family":"Hossain","sequence":"first","affiliation":[{"name":"Division of Stem Cell and Bone Marrow Transplantation, Department of Hematology and Oncology, Winship Cancer Institute, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Jaye","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P","family":"Pollack","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322"},{"name":"Atlanta Veterans Affairs Medical Center , Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alton B","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malefa L","family":"Tselanyane","sequence":"additional","affiliation":[{"name":"Division of Stem Cell and Bone Marrow Transplantation, Department of Hematology and Oncology, Winship Cancer Institute, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebenezer","family":"David","sequence":"additional","affiliation":[{"name":"Division of Stem Cell and Bone Marrow Transplantation, Department of Hematology and Oncology, Winship Cancer Institute, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Roback","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"Gewirtz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund K","family":"Waller","sequence":"additional","affiliation":[{"name":"Division of Stem Cell and Bone Marrow Transplantation, Department of Hematology and Oncology, Winship Cancer Institute, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,15]]},"reference":[{"key":"2025032410451667500_r1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3109\/10428190109057983","article-title":"Allogeneic transplantation for patients with advanced acute leukemia: a single center retrospective study of 92 patients","volume":"41","author":"Boiron","year":"2001","journal-title":"Leuk. 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