28 research outputs found
SIRT3‐dependent deacetylation exacerbates acetaminophen hepatotoxicity
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/1/embr2011121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/2/embr2011121-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/3/embr2011121.reviewer_comments.pd
Immunohistochemical Detection of Protein Adducts of 2,4-Dinitrochlorobenzene in Antigen Presenting Cells and Lymphocytes after Oral Administration to Mice: Lack of a Role of Kupffer Cells in Oral Tolerance
Metabolic Activation of Diclofenac by Human Cytochrome P450 3A4: Role of 5-Hydroxydiclofenac
Cell Ultrastructure and Distribution of Trifluoroacetylated Protein-Adducts in Early Hepatic Injury in Mice Induced by Inhalation Anesthetic, Halothane.
Immunochemical Detection and Identification of Protein Adducts of Diclofenac in the Small Intestine of Rats: Possible Role in Allergic Reactions
Metabolic Activation and Immunochemical Localization of Liver Protein Adducts of the Nonsteroidal Anti-inflammatory Drug Diclofenac
Histone demethylases UTX and JMJD3 are required for NKT cell development in mice
Abstract Background Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. Results We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected. Loss of NKT cells is cell intrinsic and not due to an insufficient selection environment. The absence of NKT cells in UTX/JMJD3-deficient mice protects mice from concanavalin A‐induced liver injury, a model of NKT‐mediated hepatitis. GO‐analysis of RNA-seq data indicates that cell cycle genes are downregulated in UTX/JMJD3-deleted NKT progenitors, and suggest that failed expansion may account for some of the cellular deficiency. The phenotype appears to be demethylase‐dependent, because UTY, a homolog of UTX that lacks catalytic function, is not sufficient to restore their development and removal of H3K27me3 by deletion of EZH2 partially rescues the defect. Conclusions NKT cell development and gene expression is sensitive to proper regulation of H3K27 methylation. The H3K27me3 demethylase enzymes, in particular UTX, promote NKT cell development, and are required for effective NKT function