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Nat Commun. 2014 Aug 8;5:4540. doi: 10.1038/ncomms5540.

Jarid2 is induced by TCR signalling and controls iNKT cell maturation.

Author information

1
Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
2
1] Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA [2].
3
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
4
1] Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA [2].
5
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
6
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.
7
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.

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.

PMID:
25105474
PMCID:
PMC4314221
DOI:
10.1038/ncomms5540
[Indexed for MEDLINE]
Free PMC Article

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