title: HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies.
abstract: The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+or CD8+T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: T cell; development; histone deacetylase 6; interleukin 17; knockout mouse.