title: Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid.
abstract: The proinflammatory cytokines interleukin 12 (IL-12) and IL-23 connect innate responses and adaptive immune responses and are also involved in autoimmune and inflammatory diseases. Here we describe an epigenetic mechanism for regulation of the genes encoding IL-12 (Il12a and Il12b; collectively called 'Il12' here) and IL-23 (Il23a and Il12b; collectively called 'Il23' here) involving the deubiquitinase Trabid. Deletion of Zranb1 (which encodes Trabid) in dendritic cells inhibited induction of the expression of Il12 and Il23 by Toll-like receptors (TLRs), which impaired the differentiation of inflammatory T cells and protected mice from autoimmune inflammation. Trabid facilitated TLR-induced histone modifications at the promoters of Il12 and Il23, which involved deubiqutination and stabilization of the histone demethylase Jmjd2d. Our findings highlight an epigenetic mechanism for the regulation of Il12 and Il23 and establish Trabid as an innate immunological regulator of inflammatory T cell responses.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, China.|Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D047468:Immunoprecipitation; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics* / Q000276:immunology; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000276:immunology; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology
chemical_list: D053759:Interleukin-23; D016601:RNA-Binding Proteins; D051193:Toll-Like Receptors; D018664:Interleukin-12; D056484:Jumonji Domain-Containing Histone Demethylases; C561303:KDM4D protein, mouse; D064570:Ubiquitin-Specific Proteases; C000608772:Zranb1 protein, mouse