{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:12:31Z","timestamp":1782720751829,"version":"3.54.5"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"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":[[2014,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-\u03b3\u2013producing Th1 CD4+ T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4+ T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4, which encode transcription factors T-bet and STAT4, respectively. Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results demonstrate that Ezh2 promotes the generation of BM-destructive Th1 cells through a mechanism of transcriptional and posttranscriptional regulation of T-bet. These results also highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1302943","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T03:17:44Z","timestamp":1398309464000},"page":"5012-5022","source":"Crossref","is-referenced-by-count":64,"title":["Ezh2 Regulates Transcriptional and Posttranslational Expression of T-bet and Promotes Th1 Cell Responses Mediating Aplastic Anemia in Mice"],"prefix":"10.1093","volume":"192","author":[{"given":"Qing","family":"Tong","sequence":"first","affiliation":[{"name":"International Joint Cancer Institute, Second Military Medical University , Shanghai 200433,","place":["China"]},{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"},{"name":"Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University , Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Mochizuki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongnian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"},{"name":"Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University , Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Mochizuki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University , Philadelphia, PA 19140"},{"name":"Institute of Health Sciences, Shanghai Institutes for Biological Sciences Chinese Academy of Sciences , Shanghai 200433,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxing","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Shanghai Institutes for Biological Sciences Chinese Academy of Sciences , Shanghai 200433,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Shanghai Institutes for Biological Sciences Chinese Academy of Sciences , Shanghai 200433,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Guo","sequence":"additional","affiliation":[{"name":"International Joint Cancer Institute, Second Military Medical University , Shanghai 200433,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hexner","sequence":"additional","affiliation":[{"name":"Department of Medicine and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, 48109"},{"name":"Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University , Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"2025032404304154900_r1","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1182\/blood-2011-12-274019","article-title":"How I treat acquired aplastic anemia","volume":"120","author":"Scheinberg","year":"2012","journal-title":"Blood"},{"key":"2025032404304154900_r2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/MOH.0b013e3282fa7470","article-title":"Aplastic anemia","volume":"15","author":"Young","year":"2008","journal-title":"Curr. 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