title: miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.
abstract: Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Thelma M
authors.initials: TM
authors.lastname: Escobar
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Chrysi
authors.initials: C
authors.lastname: Kanellopoulou
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Kugler
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Gokhul
authors.initials: G
authors.lastname: Kilaru
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Cuong K
authors.initials: CK
authors.lastname: Nguyen
authors.affiliation: Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Vijayaraj
authors.initials: V
authors.lastname: Nagarajan
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Ravikiran K
authors.initials: RK
authors.lastname: Bhairavabhotla
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Northrup
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Rami
authors.initials: R
authors.lastname: Zahr
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Burr
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Xiuhuai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: stefan.muljo@nih.gov.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Muljo
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D051700:Activating Transcription Factor 3; D002843:Chromatin; D016207:Cytokines; C547777:JARID2 protein, human; C093650:Jarid2 protein, mouse; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D063151:Polycomb Repressive Complex 2