Abstract：
:Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis1,2. Recent studies have demonstrated that Treg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets3,4. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration5,6; however, it remains unknown whether the mitochondrial respiratory chain is required for the T cell-suppression capacity, stability and survival of Treg cells. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III in mice results in the development of fatal inflammatory disease early in life, without affecting Treg cell number. Mice that lack mitochondrial complex III specifically in Treg cells displayed a loss of T cell-suppression capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III showed decreased expression of genes associated with Treg function, whereas Foxp3 expression remained stable. Loss of complex III in Treg cells increased DNA methylation as well as the metabolites 2-hydroxyglutarate (2-HG) and succinate that inhibit the ten-eleven translocation (TET) family of DNA demethylases7. Thus, Treg cells require mitochondrial complex III to maintain immune regulatory gene expression and suppressive function.
journal_name
Naturejournal_title
Natureauthors
Weinberg SE,Singer BD,Steinert EM,Martinez CA,Mehta MM,Martínez-Reyes I,Gao P,Helmin KA,Abdala-Valencia H,Sena LA,Schumacker PT,Turka LA,Chandel NSdoi
10.1038/s41586-018-0846-zsubject
Has Abstractpub_date
2019-01-01 00:00:00pages
495-499issue
7740eissn
0028-0836issn
1476-4687pii
10.1038/s41586-018-0846-zjournal_volume
565pub_type
杂志文章相关文献
NATURE文献大全abstract：:Mutants of cdc2+ can disrupt the dependency of S phase on completion of the previous mitosis. By changing the state of p34cdc2 it is possible to reprogramme a cell from entering mitosis to undergoing S phase. This leads to the proposal that the cell cycle can be considered a p34cdc2 cycle, and has implications for the...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/349388a0
更新日期：1991-01-31 00:00:00
abstract：:Cell line misidentification, contamination and poor annotation affect scientific reproducibility. Here we outline simple measures to detect or avoid cross-contamination, present a framework for cell line annotation linked to short tandem repeat and single nucleotide polymorphism profiles, and provide a catalogue of sy...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature14397
更新日期：2015-04-16 00:00:00
abstract：:Specific genes can be inactivated or mutated in the mouse germ line. The phenotypic consequences of the mutation can provide pivotal information on the function of the gene in development and maintenance of the mammalian organism. The procedure entails homologous recombination in embryonic stem cells, which, on fusion...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/348649a0
更新日期：1990-12-13 00:00:00
abstract：:Transmissible spongiform encephalopathies are associated with accumulation of PrP(Sc), a conformer of a cellular protein called PrP(C). PrP(Sc) is thought to replicate by imparting its conformation onto PrP(C) (ref. 1), yet conformational discrimination between PrP(C) and PrP(Sc) has remained elusive. Because depositi...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35044100
更新日期：2000-11-23 00:00:00
abstract：:Red colobus are one of a small number of primate species in which females have been reported to transfer between breeding groups more commonly than males. Several authors have hypothesised that in such species transference may serve to reduce the risk to females of producing offspring of lower fitness through inbreedi...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/281568a0
更新日期：1979-10-18 00:00:00
abstract：:The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chambe...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/416763a
更新日期：2002-04-18 00:00:00
abstract：:Neurotransmitter/sodium symporters (NSSs) couple the uptake of neurotransmitter with one or more sodium ions, removing neurotransmitter from the synaptic cleft. NSSs are essential to the function of chemical synapses, are associated with multiple neurological diseases and disorders, and are the targets of therapeutic ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09581
更新日期：2010-12-23 00:00:00
abstract：:B LYMPHOCYTES are key participants in the immune response because of their specificity, their ability to take up and present antigens to T cells, and their capacity to differentiate into antibody-secreting cells. To limit reactivity to self antigens, autospecific B cells can be functionally inactivated or deleted. Dev...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/354308a0
更新日期：1991-11-28 00:00:00
abstract：:Sensory systems can adapt to the conditions imposed on them. In the visual system, adapting to a pattern increases the threshold of the ability to see that pattern, and reduces the perceived contrast of the pattern above threshold. Most neurons of the striate cortex reduce their responsiveness after being stimulated f...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/355248a0
更新日期：1992-01-16 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41586-020-2064-8
更新日期：2020-03-01 00:00:00
abstract：:Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinyla...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07055
更新日期：2008-06-12 00:00:00
abstract：:Since the discovery of graphene, the family of two-dimensional materials has grown, displaying a broad range of electronic properties. Recent additions include semiconductors with spin-valley coupling, Ising superconductors that can be tuned into a quantum metal, possible Mott insulators with tunable charge-density wa...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature22391
更新日期：2017-06-07 00:00:00
abstract：:Highly correlated electronic systems--such as transition-metal oxides that are doped Mott insulators--are complex systems which exhibit puzzling phenomena, including high-temperature superconductivity and colossal magnetoresistivity. Recent studies suggest that in such systems collective electronic phenomena are impor...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35021018
更新日期：2000-08-17 00:00:00
abstract：:The vasa gene product of Drosophila melanogaster is required only in the female germ line. Progeny of females homozygous for vasa mutations lack posterior structures and pole cells. Isolation and characterization of vasa genomic and complementary DNA clones show that the transcript is abundant in the female germ line ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/335611a0
更新日期：1988-10-13 00:00:00
abstract：:Most neurons of the mammalian central nervous system (CNS) lose the ability to regenerate severed axons in vivo after a certain point in development. At least part of this loss in regenerative potential is intrinsic to neurons. Although embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age, mos...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/385434a0
更新日期：1997-01-30 00:00:00
abstract：:The distribution, accumulation and circulation of oxygen and hydrogen in Earth's interior dictate the geochemical evolution of the hydrosphere, atmosphere and biosphere. The oxygen-rich atmosphere and iron-rich core represent two end-members of the oxygen-iron (O-Fe) system, overlapping with the entire pressure-temper...
journal_title：Nature
pub_type： 历史文章,杂志文章
doi：10.1038/nature18018
更新日期：2016-06-09 00:00:00
abstract：:Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations. Population transformation using the intracellular bacterium Wolbach...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10356
更新日期：2011-08-24 00:00:00
abstract：:The paired helical filament (PHF) is the major component of the neurofibrillary deposits that form a defining neuropathological characteristic of Alzheimer's disease. PHFs are composed of microtubule-associated protein tau, in a hyperphosphorylated state. Hyperphosphorylation of tau results in its inability to bind to...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/383550a0
更新日期：1996-10-10 00:00:00
abstract：:Group selection may be defined as selection caused by the differential extinction or proliferation of groups. The socially polymorphic spider Anelosimus studiosus exhibits a behavioural polymorphism in which females exhibit either a 'docile' or 'aggressive' behavioural phenotype. Natural colonies are composed of a mix...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13811
更新日期：2014-10-16 00:00:00
abstract：:The two-dimensional electron system is a powerful laboratory for investigating the physics of interacting particles. Application of a large magnetic field produces massively degenerate quantum levels known as Landau levels; within a Landau level the kinetic energy of the electrons is suppressed, and electron-electron ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature08941
更新日期：2010-03-25 00:00:00
abstract：:One hundred years ago Albert Einstein introduced the concept of the photon. Although in the early years after 1905 the evidence for the quantum nature of light was not compelling, modern experiments--especially those using photon pairs--have beautifully confirmed its corpuscular character. Research on the quantum prop...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature03280
更新日期：2005-01-20 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/d41586-018-07501-y
更新日期：2018-11-01 00:00:00
abstract：:The delivery of therapeutic drugs to solid tumours may be impaired by structural and functional abnormalities in blood and lymphatic vessels. Here we provide evidence that proliferating cancer cells cause intratumour vessels to compress and collapse. By reducing this compressive mechanical force and opening vessels, c...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/427695a
更新日期：2004-02-19 00:00:00
abstract：:Quantum mechanical experiments in ring geometries have long fascinated physicists. Open rings connected to leads, for example, allow the observation of the Aharonov-Bohm effect, one of the best examples of quantum mechanical phase coherence. The phase coherence of electrons travelling through a quantum dot embedded in...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35101552
更新日期：2001-10-25 00:00:00
abstract：:Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (brea...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature20099
更新日期：2016-11-03 00:00:00
abstract：:The role of magnetic domains (and the walls between domains) in determining the electrical properties of ferromagnetic materials has been investigated in great detail for many years, not least because control over domains offers a means of manipulating electron spin to control charge transport in 'spintronic' devices....
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature06826
更新日期：2008-04-17 00:00:00
abstract：:Humans and cats can localize a sound source accurately if its spectrum is fairly broad and flat, as is typical of most natural sounds. However, if sounds are filtered to reduce the width of the spectrum, they result in illusions of sources that are very different from the actual locations, particularly in the up/down ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/21424
更新日期：1999-06-17 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature
pub_type： 已发布勘误
doi：10.1038/s41586-020-2789-4
更新日期：2020-10-01 00:00:00
abstract：:The RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome, suggests a funct...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/368769a0
更新日期：1994-04-21 00:00:00
abstract：:Transposable elements are viewed as 'selfish genetic elements', yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature21715
更新日期：2017-04-06 00:00:00
