BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis.

Abstract:

:Through their functional diversification, distinct lineages of CD4(+) T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma, Crohn's disease, coeliac disease, vitiligo, multiple sclerosis and type 1 diabetes. Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4(+) T cells. BACH2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within TH1, TH2 and TH17 cell lineages. These findings identify BACH2 as a key regulator of CD4(+) T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.

journal_name

Nature

journal_title

Nature

authors

Roychoudhuri R,Hirahara K,Mousavi K,Clever D,Klebanoff CA,Bonelli M,Sciumè G,Zare H,Vahedi G,Dema B,Yu Z,Liu H,Takahashi H,Rao M,Muranski P,Crompton JG,Punkosdy G,Bedognetti D,Wang E,Hoffmann V,Rivera J,Marincol

doi

10.1038/nature12199

subject

Has Abstract

pub_date

2013-06-27 00:00:00

pages

506-10

issue

7455

eissn

0028-0836

issn

1476-4687

pii

nature12199

journal_volume

498

pub_type

杂志文章

相关文献

NATURE文献大全
  • Host and viral traits predict zoonotic spillover from mammals.

    abstract::The majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, HIV, Ebola and SARS). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals f...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature22975

    authors: Olival KJ,Hosseini PR,Zambrana-Torrelio C,Ross N,Bogich TL,Daszak P

    更新日期:2017-06-29 00:00:00

  • Low-temperature hydrogen production from water and methanol using Pt/α-MoC catalysts.

    abstract::Polymer electrolyte membrane fuel cells (PEMFCs) running on hydrogen are attractive alternative power supplies for a range of applications, with in situ release of the required hydrogen from a stable liquid offering one way of ensuring its safe storage and transportation before use. The use of methanol is particularly...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature21672

    authors: Lin L,Zhou W,Gao R,Yao S,Zhang X,Xu W,Zheng S,Jiang Z,Yu Q,Li YW,Shi C,Wen XD,Ma D

    更新日期:2017-04-06 00:00:00

  • Two distinct factors are required for induction of T-cell growth.

    abstract::The molecular and cellular basis of T-lymphocyte activation remains a central question in immunology. The growth of already proliferating T cells is known to depend on T-cell growth factor (TCGF), a physiological mitogen. Noncycling T lymphocytes, however, are not sensitive to TCGF. They require a short contact with m...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/283664a0

    authors: Larsson EL,Iscove NN,Coutinho A

    更新日期:1980-02-14 00:00:00

  • Enzymatic activity of the conserved core of a group I self-splicing intron.

    abstract::Splicing of the Tetrahymena ribosomal intron was first studied by Cech et al., who subsequently demonstrated that the intron RNA catalyses its own excision from a primary transcript to yield mature ribosomal RNA. This intron shares several short conserved sequences and a common secondary structure with several other i...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/322083a0

    authors: Szostak JW

    更新日期:1986-07-03 00:00:00

  • Natural and anthropogenic variations in methane sources during the past two millennia.

    abstract::Methane is an important greenhouse gas that is emitted from multiple natural and anthropogenic sources. Atmospheric methane concentrations have varied on a number of timescales in the past, but what has caused these variations is not always well understood. The different sources and sinks of methane have specific isot...

    journal_title:Nature

    pub_type: 历史文章,杂志文章

    doi:10.1038/nature11461

    authors: Sapart CJ,Monteil G,Prokopiou M,van de Wal RS,Kaplan JO,Sperlich P,Krumhardt KM,van der Veen C,Houweling S,Krol MC,Blunier T,Sowers T,Martinerie P,Witrant E,Dahl-Jensen D,Röckmann T

    更新日期:2012-10-04 00:00:00

  • Author Correction: Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.

    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/s41586-019-1455-1

    authors: Schwörer S,Becker F,Feller C,Baig AH,Köber U,Henze H,Kraus JM,Xin B,Lechel A,Lipka DB,Varghese CS,Schmidt M,Rohs R,Aebersold R,Medina KL,Kestler HA,Neri F,von Maltzahn J,Tümpel S,Rudolph KL

    更新日期:2019-08-01 00:00:00

  • Sub-piconewton force fluctuations of actomyosin in vitro.

    abstract::A new system has been developed for measuring the forces produced by a small number (less than 5-150) of myosin molecules interacting with a single actin filament in vitro. The technique can resolve forces of less than a piconewton and has a time resolution in the submillisecond range. It can thus detect fluctuations ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/352301a0

    authors: Ishijima A,Doi T,Sakurada K,Yanagida T

    更新日期:1991-07-25 00:00:00

  • Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells.

    abstract::The rod and cone transducins are specific G proteins originally thought to be present only in photoreceptor cells of the vertebrate retina. Transducins convert light stimulation of photoreceptor opsins into activation of cyclic GMP phosphodiesterase (reviewed in refs. 5-7). A transducin-like G protein, gustducin, has ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/376080a0

    authors: Ruiz-Avila L,McLaughlin SK,Wildman D,McKinnon PJ,Robichon A,Spickofsky N,Margolskee RF

    更新日期:1995-07-06 00:00:00

  • An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.

    abstract::Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation. PGX was 30 times more potent in this respect than prostaglandin E1. PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vess...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/263663a0

    authors: Moncada S,Gryglewski R,Bunting S,Vane JR

    更新日期:1976-10-21 00:00:00

  • Role of spectral detail in sound-source localization.

    abstract::Sounds heard over headphones are typically perceived inside the head (internalized), unlike real sound sources which are perceived outside the head (externalized). If the acoustical waveforms from a real sound source are reproduced precisely using headphones, auditory images are appropriately externalized and localize...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/25526

    authors: Kulkarni A,Colburn HS

    更新日期:1998-12-24 00:00:00

  • An intermediate-mass black hole of over 500 solar masses in the galaxy ESO 243-49.

    abstract::Ultraluminous X-ray sources are extragalactic objects located outside the nucleus of the host galaxy with bolometric luminosities exceeding 10(39) erg s(-1). These extreme luminosities-if the emission is isotropic and below the theoretical (Eddington) limit, where the radiation pressure is balanced by the gravitationa...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature08083

    authors: Farrell SA,Webb NA,Barret D,Godet O,Rodrigues JM

    更新日期:2009-07-02 00:00:00

  • Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors.

    abstract::Transparent electronic devices formed on flexible substrates are expected to meet emerging technological demands where silicon-based electronics cannot provide a solution. Examples of active flexible applications include paper displays and wearable computers. So far, mainly flexible devices based on hydrogenated amorp...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03090

    authors: Nomura K,Ohta H,Takagi A,Kamiya T,Hirano M,Hosono H

    更新日期:2004-11-25 00:00:00

  • The GTP-binding protein, Go, regulates neuronal calcium channels.

    abstract::In neuronal cells, opioid peptides and opiates inhibit neurotransmitter release, which is a calcium-dependent process. They also inhibit adenylyl cyclase, presumably via the membrane signal-transducing component, Gi, a guanine nucleotide-binding protein (G-protein). No causal relationship between these two events has ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/325445a0

    authors: Hescheler J,Rosenthal W,Trautwein W,Schultz G

    更新日期:1987-01-29 00:00:00

  • Magnetoelectrics: is CdCr2S4 a multiferroic relaxor?

    abstract::Materials showing simultaneous ferroelectric and magnetic ordering are attracting a great deal of interest because of their unusual physics and potential applications. Hemberger et al. have reported relaxor-like dielectric properties and colossal magnetocapacitance (in excess of 500%) for the cubic spinel compound CdC...

    journal_title:Nature

    pub_type: 评论,杂志文章

    doi:10.1038/nature06156

    authors: Catalan G,Scott JF

    更新日期:2007-08-23 00:00:00

  • Measurement of the quantum geometric tensor and of the anomalous Hall drift.

    abstract::Topological physics relies on the structure of the eigenstates of the Hamiltonians. The geometry of the eigenstates is encoded in the quantum geometric tensor1-comprising the Berry curvature2 (crucial for topological matter)3 and the quantum metric4, which defines the distance between the eigenstates. Knowledge of the...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-1989-2

    authors: Gianfrate A,Bleu O,Dominici L,Ardizzone V,De Giorgi M,Ballarini D,Lerario G,West KW,Pfeiffer LN,Solnyshkov DD,Sanvitto D,Malpuech G

    更新日期:2020-02-01 00:00:00

  • Photobombing stars lead to cosmic false identity.

    abstract:: ...

    journal_title:Nature

    pub_type: 新闻

    doi:10.1038/d41586-018-07413-x

    authors:

    更新日期:2018-11-01 00:00:00

  • Ancestral echinoderms from the Chengjiang deposits of China.

    abstract::Deuterostomes are a remarkably diverse super-phylum, including not only the chordates (to which we belong) but groups as disparate as the echinoderms and the hemichordates. The phylogeny of deuterostomes is now achieving some degree of stability, especially on account of new molecular data, but this leaves as conjectu...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02648

    authors: Shu DG,Morris SC,Han J,Zhang ZF,Liu JN

    更新日期:2004-07-22 00:00:00

  • Pattern recognition and active vision in chickens.

    abstract::Recognition of objects or environmental landmarks is problematic because appearance can vary widely depending on illumination, viewing distance, angle of view and so on. Storing a separate image or 'template' for every possible view requires vast numbers to be stored and scanned, has a high probability of recognition ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35001064

    authors: Dawkins MS,Woodington A

    更新日期:2000-02-10 00:00:00

  • Neuroscience in the era of functional genomics and systems biology.

    abstract::Advances in genetics and genomics have fuelled a revolution in discovery-based, or hypothesis-generating, research that provides a powerful complement to the more directly hypothesis-driven molecular, cellular and systems neuroscience. Genetic and functional genomic studies have already yielded important insights into...

    journal_title:Nature

    pub_type: 杂志文章,评审

    doi:10.1038/nature08537

    authors: Geschwind DH,Konopka G

    更新日期:2009-10-15 00:00:00

  • The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency.

    abstract::The TGFβ pathway has essential roles in embryonic development, organ homeostasis, tissue repair and disease. These diverse effects are mediated through the intracellular effectors SMAD2 and SMAD3 (hereafter SMAD2/3), whose canonical function is to control the activity of target genes by interacting with transcriptiona...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature25784

    authors: Bertero A,Brown S,Madrigal P,Osnato A,Ortmann D,Yiangou L,Kadiwala J,Hubner NC,de Los Mozos IR,Sadée C,Lenaerts AS,Nakanoh S,Grandy R,Farnell E,Ule J,Stunnenberg HG,Mendjan S,Vallier L

    更新日期:2018-03-08 00:00:00

  • A new troodontid dinosaur from China with avian-like sleeping posture.

    abstract::Discovering evidence of behaviour in fossilized vertebrates is rare. Even rarer is evidence of behaviour in non-avialan dinosaurs that directly relates to stereotypical behaviour seen in extant birds (avians) and not previously predicted in non-avialan dinosaurs. Here we report the discovery of a new troodontid taxon ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02898

    authors: Xu X,Norell MA

    更新日期:2004-10-14 00:00:00

  • Role of poly(ADP-ribose) formation in DNA repair.

    abstract::The abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+). This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD(+)-binding domain by a short region containing several ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/356356a0

    authors: Satoh MS,Lindahl T

    更新日期:1992-03-26 00:00:00

  • Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor.

    abstract::T lymphocytes are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a resul...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/341746a0

    authors: Kaye J,Hsu ML,Sauron ME,Jameson SC,Gascoigne NR,Hedrick SM

    更新日期:1989-10-26 00:00:00

  • Rapid regeneration of the actin-myosin power stroke in contracting muscle.

    abstract::At the molecular level, muscle contraction is the result of cyclic interaction between myosin crossbridges, which extend from the thick filament, and the thin filament, which consists mainly of actin. The energy for work done by a single crossbridge during a cycle of attachment, generation of force, shortening and det...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/355638a0

    authors: Lombardi V,Piazzesi G,Linari M

    更新日期:1992-02-13 00:00:00

  • Conservation of the sizes for one but not another class of exons in two chick collagen genes.

    abstract::Type III collagen is often found in the same tissues as type I collagen, yet the function and nature of the fibrils formed by the two collagens differ markedly. To understand the evolutionary history of the collagen gene family in more detail, we isolated the gene for type III collagen and compared its structure with ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/310333a0

    authors: Yamada Y,Liau G,Mudryj M,Obici S,de Crombrugghe B

    更新日期:1984-07-26 00:00:00

  • Hypothalamic regulation of sleep and circadian rhythms.

    abstract::A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal s...

    journal_title:Nature

    pub_type: 杂志文章,评审

    doi:10.1038/nature04284

    authors: Saper CB,Scammell TE,Lu J

    更新日期:2005-10-27 00:00:00

  • Non-thermal melting in semiconductors measured at femtosecond resolution.

    abstract::Ultrafast time-resolved optical spectroscopy has revealed new classes of physical, chemical and biological reactions, in which directed, deterministic motions of atoms have a key role. This contrasts with the random, diffusive motion of atoms across activation barriers that typically determines kinetic rates on slower...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35065045

    authors: Rousse A,Rischel C,Fourmaux S,Uschmann I,Sebban S,Grillon G,Balcou P,Förster E,Geindre JP,Audebert P,Gauthier JC,Hulin D

    更新日期:2001-03-01 00:00:00

  • The genomic history of southeastern Europe.

    abstract::Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeast...

    journal_title:Nature

    pub_type: 历史文章,杂志文章

    doi:10.1038/nature25778

    authors: Mathieson I,Alpaslan-Roodenberg S,Posth C,Szécsényi-Nagy A,Rohland N,Mallick S,Olalde I,Broomandkhoshbacht N,Candilio F,Cheronet O,Fernandes D,Ferry M,Gamarra B,Fortes GG,Haak W,Harney E,Jones E,Keating D,Krause-Kyora

    更新日期:2018-03-08 00:00:00

  • Computational design of ligand-binding proteins with high affinity and selectivity.

    abstract::The ability to design proteins with high affinity and selectivity for any given small molecule is a rigorous test of our understanding of the physiochemical principles that govern molecular recognition. Attempts to rationally design ligand-binding proteins have met with little success, however, and the computational d...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature12443

    authors: Tinberg CE,Khare SD,Dou J,Doyle L,Nelson JW,Schena A,Jankowski W,Kalodimos CG,Johnsson K,Stoddard BL,Baker D

    更新日期:2013-09-12 00:00:00

  • Global covariation of carbon turnover times with climate in terrestrial ecosystems.

    abstract::The response of the terrestrial carbon cycle to climate change is among the largest uncertainties affecting future climate change projections. The feedback between the terrestrial carbon cycle and climate is partly determined by changes in the turnover time of carbon in land ecosystems, which in turn is an ecosystem p...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature13731

    authors: Carvalhais N,Forkel M,Khomik M,Bellarby J,Jung M,Migliavacca M,Mu M,Saatchi S,Santoro M,Thurner M,Weber U,Ahrens B,Beer C,Cescatti A,Randerson JT,Reichstein M

    更新日期:2014-10-09 00:00:00