{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:57:59Z","timestamp":1791291479186,"version":"4.3.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T00:00:00Z","timestamp":1423180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["MRSG-11-149-01-LIB"],"award-info":[{"award-number":["MRSG-11-149-01-LIB"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"S. National Institutes of Health (NIH) National Heart, Lung, and Blood Institute","award":["K08 HL11654701A1"],"award-info":[{"award-number":["K08 HL11654701A1"]}]},{"name":"American Society for Blood and Marrow Transplantation\/Bristol-Myers Squibb New Investigator"},{"DOI":"10.13039\/100000054","name":"NIH National Cancer Institute","doi-asserted-by":"crossref","award":["R01 CA132197"],"award-info":[{"award-number":["R01 CA132197"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH National Heart, Lung, and Blood Institute","award":["R01 HL114994"],"award-info":[{"award-number":["R01 HL114994"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Th17 cells contribute to severe GVHD in murine bone marrow transplantation. Targeted deletion of the ROR\u03b3t transcription factor or blockade of the JAK2-STAT3 axis suppresses IL-17 production and alloreactivity by Th17 cells. Here, we show that pSTAT3 Y705 is increased significantly in CD4+ T cells among human recipients of allogeneic HCT before the onset of Grade II\u2013IV acute GVHD. Examination of target-organ tissues at the time of GVHD diagnosis indicates that the amount of ROR\u03b3t + Th17 cells is significantly higher in severe GVHD. Greater accumulation of tissue-resident Th17 cells also correlates with the use of MTX- compared with Rapa-based GVHD prophylaxis, as well as a poor therapeutic response to glucocorticoids. ROR\u03b3t is optimally suppressed by concurrent neutralization of TORC1 with Rapa and inhibition of STAT3 activation with S3I-201, supporting that mTOR- and STAT3-dependent pathways converge upon ROR\u03b3t gene expression. Rapa-resistant T cell proliferation can be totally inhibited by STAT3 blockade during initial allosensitization. We conclude that STAT3 signaling and resultant Th17 tissue accumulation are closely associated with acute GVHD onset, severity, and treatment outcome. Future studies are needed to validate the association of STAT3 activity in acute GVHD. Novel GVHD prevention strategies that incorporate dual STAT3 and mTOR inhibition merit investigation.<\/jats:p>","DOI":"10.1189\/jlb.5a1114-532rr","type":"journal-article","created":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T20:59:32Z","timestamp":1423256372000},"page":"807-819","source":"Crossref","is-referenced-by-count":47,"title":["CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response"],"prefix":"10.1093","volume":"97","author":[{"given":"Brian C","family":"Betts","sequence":"first","affiliation":[{"name":"Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"},{"name":"Department of Immunology, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M","family":"Sagatys","sequence":"additional","affiliation":[{"name":"Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anandharaman","family":"Veerapathran","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"},{"name":"Department of Immunology, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Analytic Microscopy Core, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Beato","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"},{"name":"Department of Immunology, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshani R","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binglin","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, H. Lee Moffitt Cancer Center , Tampa, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongphil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, H. 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