title: Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells.
abstract: The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as negative regulators of transcriptional regulation, and in this context, the primarily nuclear protein HDAC11 was shown to repress il-10 gene transcriptional activity in antigen-presenting cells (APCs). Here we report that another HDAC, HDAC6, primarily a cytoplasmic protein, associates with HDAC11 and modulates the expression of IL-10 as a transcriptional activator. To our knowledge, this is the first demonstration of two different HDACs being recruited to the same gene promoter to dictate divergent transcriptional responses. This dynamic interaction results in dynamic changes in the expression of IL-10 and might help to explain the intrinsic plasticity of the APC to determine T-cell activation versus T-cell tolerance.
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Fengdong
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Maritza
authors.initials: M
authors.lastname: Lienlaf
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Patricio
authors.initials: P
authors.lastname: Perez-Villarroel
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: All Children's Research Institute, All Children's Hospital-Johns Hopkins Medicine, St. Petersburg, FL.|Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Calvin
authors.initials: C
authors.lastname: Lee
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Karrune
authors.initials: K
authors.lastname: Woan
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: David
authors.initials: D
authors.lastname: Woods
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Tessa
authors.initials: T
authors.lastname: Knox
authors.affiliation: Drug Discovery Program Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL.
authors.forename: Joel
authors.initials: J
authors.lastname: Bergman
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.affiliation: Drug Discovery Program Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL.
authors.forename: Alan
authors.initials: A
authors.lastname: Kozikowski
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Sotomayor
authors.affiliation: Departments of Immunology and Malignant Hematology, Tampa, FL.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Villagra
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D034741:RNA, Small Interfering; D016753:Interleukin-10; C528111:Hdac11 protein, mouse; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: Antigen presenting cells; HDAC11; HDAC6; IL-10; Tolerance
references.citation: Nat Rev Immunol. 2010 Mar;10(3):170-81
references.pmid: 20154735
references.citation: J Biol Chem. 2006 Aug 11;281(32):22695-706
references.pmid: 16772287
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: J Immunol. 1991 Oct 15;147(8):2816-23
references.pmid: 1918995
references.citation: Mol Cell. 2007 Jul 20;27(2):197-213
references.pmid: 17643370
references.citation: J Mol Biol. 2010 Jul 16;400(3):284-94
references.pmid: 20493879
references.citation: Nature. 2007 Jun 21;447(7147):972-8
references.pmid: 17538624
references.citation: Immunity. 2008 Apr;28(4):546-58
references.pmid: 18387831
references.citation: Immunol Cell Biol. 2012 Jan;90(1):55-65
references.pmid: 22105512
references.citation: Biochem J. 2003 Mar 15;370(Pt 3):737-49
references.pmid: 12429021
references.citation: J Biol Chem. 2002 Jul 12;277(28):25748-55
references.pmid: 11948178
references.citation: Eur J Immunol. 2007 Nov;37(11):3164-75
references.pmid: 17948265
references.citation: J Immunol. 2006 Jul 15;177(2):1282-8
references.pmid: 16818788
references.citation: J Biomed Biotechnol. 2011;2011:875824
references.pmid: 21076528
references.citation: Immunity. 2008 Apr;28(4):468-76
references.pmid: 18400189
references.citation: Nat Rev Mol Cell Biol. 2008 Mar;9(3):206-18
references.pmid: 18292778
references.citation: Mol Cell Biol. 2011 May;31(10):2066-78
references.pmid: 21444725
references.citation: J Leukoc Biol. 2005 Jan;77(1):3-15
references.pmid: 15522916
references.citation: Trends Cell Biol. 2008 Jun;18(6):291-7
references.pmid: 18472263
references.citation: Nat Rev Immunol. 2009 Oct;9(10):692-703
references.pmid: 19859064
references.citation: J Biol Chem. 2009 Apr 24;284(17):11446-53
references.pmid: 19276081
references.citation: Nat Immunol. 2009 Jan;10(1):92-100
references.pmid: 19011628
references.citation: Oncogene. 2007 Aug 13;26(37):5468-76
references.pmid: 17694087
references.citation: Mol Cell Biol. 2008 Mar;28(5):1688-701
references.pmid: 18180281
references.citation: PLoS Genet. 2010 Dec 09;6(12):e1001240
references.pmid: 21170301
references.citation: Annu Rev Immunol. 2007;25:267-96
references.pmid: 17134371
references.citation: Immunity. 2003 May;18(5):605-17
references.pmid: 12753738
references.citation: J Med Chem. 2008 Aug 14;51(15):4370-3
references.pmid: 18642892
references.citation: Immunity. 2004 Apr;20(4):417-28
references.pmid: 15084271
references.citation: Nat Immunol. 2009 Nov;10(11):1178-84
references.pmid: 19783988