T follicular helper cell-dependent clearance of a persistent virus infection requires T cell expression of the histone demethylase UTX
Open accessAbstract
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.
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Reduced expression of the UTX gene is associated with impairment of the T-cell mediated immune response and chronic viral infections in TS.
“In addition to these anatomical differences, reduced expression of the UTX gene is associated with impairment of the T-cell mediated immune response and chronic viral infections.656-658”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [656]
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References 60 · Cited by 83
- Authors
- Cook, K. D., Shpargel, K. B., Starmer, J., Whitfield-Larry, F., Conley, B., Allard, D. E., Rager, J. E., Fry, R. C., Davenport, M. L., Magnuson, T., Whitmire, J. K., & Su, M. A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Whitmire, Jason K.
- Su, Maureen A.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 43
- Issue
- 4
- Pages
- 703-714
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4731234
- OpenAlex
- W2108194358
- Cited by
- 83
- References
- 60
- Citations by year
- 2025: 8 · 2024: 4 · 2023: 12 · 2022: 11 · 2021: 9 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 5
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- University of North Carolina (TTSA004P2, T32 AI7273-27, R01 NS079683, R01 GM10974, R56 AI110682, R01 AI074862)
- North Carolina Translational and Clinical Sciences Institute, University of North Carolina at Chapel Hill (TTSA004P2, T32 AI7273-27, R01 NS079683, R01 GM10974, R56 AI110682, R01 AI074862)
- National Institutes of Health (TTSA004P2, T32 AI7273-27, R01 NS079683, R01 GM10974, R56 AI110682, R01 AI074862)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- KDM6A, T follicular helper cells, chronic viral infection, lymphocytic choriomeningitis virus, germinal center, B cell antibody response, IgG, histone methylation, epigenetic regulation, Turner syndrome, T cell differentiation
- MeSH terms
- Animals, Antibodies, Viral, Cell Differentiation, Female, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Histones, Humans, Immunologic Memory, Lymphocyte Cooperation, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Methylation, Nuclear Proteins, Otitis Media, Protein Processing, Post-Translational, Species Specificity, Transcription, Genetic, Turner Syndrome, Viremia, Virulence, T-Lymphocyte Subsets, Models, Immunological, Gene Dosage, Genetic Predisposition to Disease, X Chromosome Inactivation, Mice, Interleukin-6 Receptor alpha Subunit, Receptors, CXCR5, Histone Demethylases
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