| Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells. | |
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MedLine Citation:
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PMID: 21444725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Foxp3(+) T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3(+) Tregs express multiple histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression, and protein function. Pan-HDAC inhibitors developed for oncologic applications enhance Treg production and Treg suppression function but have limited nononcologic utility given their broad actions and various side effects. We show, using HDAC6-deficient mice and wild-type (WT) mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully major histocompatibility complex (MHC)-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein heat shock protein 90 (HSP90). Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection. |
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Authors:
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Edwin F de Zoeten; Liqing Wang; Kyle Butler; Ulf H Beier; Tatiana Akimova; Hong Sai; James E Bradner; Ralph Mazitschek; Alan P Kozikowski; Patrick Matthias; Wayne W Hancock |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-28 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 31 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-28 Completed Date: 2011-06-27 Revised Date: 2012-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2066-78 Citation Subset: IM |
Affiliation:
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Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104-4318, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE27896 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anilides
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pharmacology Animals Autoimmunity Blotting, Western Colitis / metabolism Disease Progression Flow Cytometry Forkhead Transcription Factors / analysis Gene Targeting Graft Rejection / prevention & control HSP90 Heat-Shock Proteins / antagonists & inhibitors, genetics, metabolism* Histone Deacetylase Inhibitors / pharmacology Histone Deacetylases / genetics, metabolism* Hydroxamic Acids / pharmacology Immunoprecipitation Indoles / pharmacology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Microarray Analysis Molecular Sequence Data Polymerase Chain Reaction T-Lymphocytes, Regulatory / drug effects, immunology*, metabolism Transplantation Tolerance |
| Grant Support | |
ID/Acronym/Agency:
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K08 CA128972-04/CA/NCI NIH HHS; K08 CA128972-05/CA/NCI NIH HHS; K08DK080189/DK/NIDDK NIH HHS; P01AI073489/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anilides; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/HSP90 Heat-Shock Proteins; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Indoles; 0/tubacin; 0/tubastatin A; EC 3.5.1.98/Hdac6 protein, mouse; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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