{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:59:10Z","timestamp":1792205950233,"version":"4.4.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation. Valproic acid (VPA) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models. Using well-characterized mouse models of MHC-mismatched transplantation, we studied the effects of VPA on GVHD severity and graft-versus-leukemia (GVL) activity. Administration of VPA significantly attenuated the clinical severity of GVHD, the histopathology of GVHD-involved organs, and the overall mortality from GVHD. VPA downregulated Th1 and Th17 cell responses and cytokine production in vitro and in vivo, whereas its effect on GVHD was regulatory T cell independent. The effect of VPA was related to its ability to directly reduce the activity of Akt, an important regulator of T cell immune responses. Importantly, when mice received lethal doses of host-type acute leukemia cells, administration of VPA did not impair GVL activity and resulted in significantly improved leukemia-free survival. These findings reveal a unique role for VPA as a histone deacetylase inhibitor in reducing the donor CD4+ T cells that contribute to GVHD, which may provide a strategy to reduce GVHD while preserving the GVL effect.<\/jats:p>","DOI":"10.4049\/jimmunol.1500578","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T02:00:07Z","timestamp":1437012007000},"page":"1849-1857","source":"Crossref","is-referenced-by-count":27,"title":["Valproic Acid Ameliorates Graft-versus-Host Disease by Downregulating Th1 and Th17 Cells"],"prefix":"10.1093","volume":"195","author":[{"given":"Jun","family":"Long","sequence":"first","affiliation":[{"name":"State Key Laboratory for Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]},{"name":"Department of Hematology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200025 ,","place":["China"]},{"name":"Shanghai Institute of 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