Evidence map›Paper›PMID 36928413›Full record

ArticleNature immunology2023

The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences.

Mandy I Cheng, Joey H Li, Luke Riggan, Bryan Chen, Rana Yakhshi Tafti, Scott Chin, Feiyang Ma, Matteo Pellegrini, Haley Hrncir, Arthur P Arnold and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
17.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 107 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Mandy I ChengDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8915-0296
Joey H LiDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Luke RigganDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Bryan ChenDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-0046-2283
Rana Yakhshi TaftiDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Scott ChinDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Feiyang MaDepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6260-0787
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
Haley HrncirDepartment of Integrative Biology & Physiology, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA.
Arthur P ArnoldDepartment of Integrative Biology & Physiology, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA.
Timothy E O'SullivanDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. tosullivan@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-1435-8188
Maureen A SuDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. masu@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-3680-9982
University of California, Los Angeles · US

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZACK, JEROME A. · 1991 to 2018
$39.9M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Regulation of CD8+ T cell responses to chronic virus infectionR01AI143894 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WHITMIRE, JASON KYLE · 2019 to 2023
$2.5M
Transcriptional mechanisms of natural killer cell responses during mouse cytomegalovirus infectionR01AI145997 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI O'SULLIVAN, TIMOTHY E · 2019 to 2023
$2.3M
Coupling neuroimaging with CLARITY and single cell genomics to dissect sex differences in the developing brainR01HD100298 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, LERCH, JASON P. · 2020 to 2024
$2.2M
Autoimmune Mechanisms in Peripheral NeuropathyR01NS107851 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SCHERER, STEVEN SIMON, SU, MAUREEN A · 2018 to 2021
$2.0M
Epigenetic Mechanisms in Type 1 DiabetesR01DK119445 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SU, MAUREEN A · 2020 to 2023
$1.5M
Dermatology Scientist Training ProgramT32AR071307 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2017 to 2021
$1.1M
NIAID NIH HHS P30 AI028697NIAID NIH HHS R01 AI143894NIAID NIH HHS R01 AI145997NIAID NIH HHS T32 AI007323NIAMS NIH HHS T32 AR071307NICHD NIH HHS R01 HD100298NIDDK NIH HHS R01 DK119445NIGMS NIH HHS T32 GM007185NIGMS NIH HHS T32 GM008042NINDS NIH HHS R01 NS107851
6 · The paper itself

Abstract

Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.

Indexed as

Genes, X-LinkedSex CharacteristicsAnimalsEpigenesis, GeneticFemaleHistone DemethylasesHumansKiller Cells, NaturalMaleMiceHistone DemethylasesUtx protein, mouse

Identifiers

PMID36928413
PMCPMC12882737
OpenAlexW4327568924

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.