Nature Medicine ：抗击过度免疫反应的药物
组蛋白去乙酰酶(HDAC)抑制剂是美国食品和药物管理局FDA批准的一种癌症治疗药物，Wayne Hancock和同事却发现，这种药物还可能抑制过度的免疫反应，这一最新的研究成果发表在11月号的《自然—医学》期刊上。
免疫系统的过度反应会导致一系列的问题，如炎症性肠病和对移植器官的排斥。Hancock和同事发现，HDAC抑制剂能够激活调控性T细胞，这种细胞因为能抑制其他的免疫反应，因而也被称为抑制性T细胞。因此，HDAC抑制剂降低了炎症性肠病的症状，并能预防对心脏和胰腺移植的排斥。
新发现预测，HDAC抑制剂也许还能对付与免疫活性相关的疾病，如多发性硬化症等自体免疫性疾病。（科学时报）
原始出处:
Nature Medicine
Published online: 7 October 2007 | doi:10.1038/nm1652
Deacetylase inhibition promotes the generation and function of regulatory T cells
Ran Tao1, Edwin F de Zoeten2,3, Engin Özkaynak1,4, Chunxia Chen1, Liqing Wang1, Paige M Porrett3, Bin Li4, Laurence A Turka3, Eric N Olson5, Mark I Greene4, Andrew D Wells1,4 & Wayne W Hancock1,4
Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive function of regulatory T cells (Treg cells). Although Treg cells express multiple HDACs, HDAC9 proved particularly important in regulating Foxp3-dependent suppression. Optimal Treg function required acetylation of several lysines in the forkhead domain of Foxp3, and Foxp3 acetylation enhanced binding of Foxp3 to the Il2 promoter and suppressed endogenous IL-2 production. HDACi therapy in vivo enhanced Treg-mediated suppression of homeostatic proliferation, decreased inflammatory bowel disease through Treg-dependent effects, and, in conjunction with a short course of low-dose rapamycin, induced permanent, Treg-dependent cardiac and islet allograft survival and donor-specific allograft tolerance. Our data show that use of HDACi allows the beneficial pharmacologic enhancement of both the numbers and suppressive function of Foxp3+ Treg cells.
- Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Studies of Pediatric Liver Diseases, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-4318, USA.
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-4318, USA.
- Department of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-6082, USA.
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-6082, USA.
- Department of Molecular Biology,University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Correspondence to: Wayne W Hancock1,4 e-mail: whancock@mail.med.upenn.edu
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