Format

Send to

Choose Destination
Immunity. 2015 Oct 20;43(4):703-14. doi: 10.1016/j.immuni.2015.09.002. Epub 2015 Sep 29.

T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX.

Author information

1
Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
2
Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
3
Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
4
Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
5
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
6
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
7
Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA. Electronic address: jwhitmir@email.unc.edu.
8
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, 120 Mason Farm Road, Chapel Hill, NC 27599, USA. Electronic address: masu@email.unc.edu.

Abstract

Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential for B cell antibody generation and the resolution of chronic viral infections. Mice with a T cell-specific UTX deletion had fewer Tfh cells, reduced germinal center responses, lacked virus-specific immunoglobulin G (IgG), and were unable to resolve chronic lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed decreased expression of interleukin-6 receptor-α and other Tfh cell-related genes that were associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection.

PMID:
26431949
PMCID:
PMC4731234
DOI:
10.1016/j.immuni.2015.09.002
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center