Histone demethylases UTX and JMJD3 are required for NKT cell development in miceReportar como inadecuado




Histone demethylases UTX and JMJD3 are required for NKT cell development in mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cell and Bioscience

, 7:25

First Online: 17 May 2017Received: 13 April 2017Accepted: 02 May 2017DOI: 10.1186-s13578-017-0152-8

Cite this article as: Northrup, D., Yagi, R., Cui, K. et al. Cell Biosci 2017 7: 25. doi:10.1186-s13578-017-0152-8

Abstract

BackgroundNatural killer NKT 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.

ResultsWe 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.

ConclusionsNKT 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.

Electronic supplementary materialThe online version of this article doi:10.1186-s13578-017-0152-8 contains supplementary material, which is available to authorized users.

Daniel Northrup and Ryoji Yagi contributed equally to this work





Autor: Daniel Northrup - Ryoji Yagi - Kairong Cui - William R. Proctor - Chaochen Wang - Katarzyna Placek - Lance R. Pohl - Rong

Fuente: https://link.springer.com/







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