title: Jarid2 is induced by TCR signalling and controls iNKT cell maturation.
abstract: Jarid2 is a reported component of three lysine methyltransferase complexes, polycomb repressive complex 2 (PRC2) that methylates histone 3 lysine 27 (H3K27), and GLP-G9a and SETDB1 complexes that methylate H3K9. Here we show that Jarid2 is upregulated upon TCR stimulation and during positive selection in the thymus. Mice lacking Jarid2 in T cells display an increase in the frequency of IL-4-producing promyelocytic leukemia zinc finger (PLZF)(hi) immature invariant natural killer T (iNKT) cells and innate-like CD8(+) cells; Itk-deficient mice, which have a similar increase of innate-like CD8(+) cells, show blunted upregulation of Jarid2 during positive selection. Jarid2 binds to the Zbtb16 locus, which encodes PLZF, and thymocytes lacking Jarid2 show increased PLZF and decreased H3K9me3 levels. Jarid2-deficient iNKT cells perturb Th17 differentiation, leading to reduced Th17-driven autoimmune pathology. Our results establish Jarid2 as a novel player in iNKT cell maturation that regulates PLZF expression by modulating H3K9 methylation.
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Pereira
authors.affiliation: 1] Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA [2].
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martinez
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Engel
authors.affiliation: 1] Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA [2].
authors.forename: Fernando
authors.initials: F
authors.lastname: Cruz-Guilloty
authors.affiliation: 1] Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA [2].
authors.forename: Bianca A
authors.initials: BA
authors.lastname: Barboza
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Ageliki
authors.initials: A
authors.lastname: Tsagaratou
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Chan-Wang J
authors.initials: CW
authors.lastname: Lio
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Berg
authors.affiliation: Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.affiliation: 1] Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA [2].
authors.forename: Hozefa S
authors.initials: HS
authors.lastname: Bandukwala
authors.affiliation: 1] Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA [2] Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006657:Histones / Q000737:chemistry; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland / Q000378:metabolism; D015854:Up-Regulation; D016335:Zinc Fingers; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006657:Histones; D015847:Interleukin-4; D051741:Kruppel-Like Transcription Factors; D037181:Lectins, C-Type; D008239:Lysine; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C093650:Jarid2 protein, mouse; C513267:Zbtb16 protein, mouse
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