Abstract：
:Tumor-associated macrophages (TAMs) play an important role in the immune response to cancer, but the mechanisms by which the tumor microenvironment controls TAMs and T cell immunity are not completely understood. Here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor (AHR) in TAMs to modulate their function and T cell immunity. AHR promotes CCR2 expression, driving TAM recruitment in response to CCL2. AHR also drives the expression of KLF4 and suppresses NF-κB activation in TAMs. Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. In humans, the expression of AHR and CD39 was highest in grade 4 glioma, and high AHR expression was associated with poor prognosis. In summary, AHR and CD39 expressed in TAMs participate in the regulation of the immune response in glioblastoma and constitute potential targets for immunotherapy.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Takenaka MC,Gabriely G,Rothhammer V,Mascanfroni ID,Wheeler MA,Chao CC,Gutiérrez-Vázquez C,Kenison J,Tjon EC,Barroso A,Vandeventer T,de Lima KA,Rothweiler S,Mayo L,Ghannam S,Zandee S,Healy L,Sherr D,Farez MF,Prat A,doi
10.1038/s41593-019-0370-ysubject
Has Abstractpub_date
2019-05-01 00:00:00pages
729-740issue
5eissn
1097-6256issn
1546-1726pii
10.1038/s41593-019-0370-yjournal_volume
22pub_type
杂志文章abstract：:Continuous, predictable events and spontaneous events may coincide in the visual environment. For a continuously moving object, the brain compensates for delays in transmission between a retinal event and neural responses in higher visual areas. Here we show that it similarly compensated for other smoothly changing fe...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/74865
更新日期：2000-05-01 00:00:00
abstract：:The morphological transition of growth cones to synaptic boutons characterizes synaptogenesis. Here we have isolated mutations in immaculate connections (imac; CG8566), a previously uncharacterized Drosophila gene encoding a member of the Kinesin-3 family. Whereas earlier studies in Drosophila implicated Kinesin-1 in ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1936
更新日期：2007-08-01 00:00:00
abstract：:Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antago...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn769
更新日期：2001-12-01 00:00:00
abstract：:Neuroligins are postsynaptic cell adhesion molecules that are important for synaptic function through their trans-synaptic interaction with neurexins (NRXNs). The localization and synaptic effects of neuroligin-1 (NL-1, also called NLGN1) are specific to excitatory synapses with the capacity to enhance excitatory syna...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3601
更新日期：2014-01-01 00:00:00
abstract：:To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0530-0
更新日期：2019-12-01 00:00:00
abstract：:Perturbations of astrocytes trigger neurodegeneration in several diseases, but the glial cell-intrinsic mechanisms that induce neurodegeneration remain poorly understood. We found that a protein complex of α2-Na/K ATPase and α-adducin was enriched in astrocytes expressing mutant superoxide dismutase 1 (SOD1), which ca...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3853
更新日期：2014-12-01 00:00:00
abstract：:Some neurons in auditory cortex respond to recent stimulus history by adapting their response functions to track stimulus statistics directly, as might be expected. In contrast, some neurons respond to loud sounds by adjusting their response functions away from high intensities and consequently remain sensitive to sof...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2201
更新日期：2008-11-01 00:00:00
abstract：:We investigated the regulation of T-type channels by Rho-associated kinase (ROCK). Activation of ROCK via the endogenous ligand lysophosphatidic acid (LPA) reversibly inhibited the peak current amplitudes of rat Ca(v)3.1 and Ca(v)3.3 channels without affecting the voltage dependence of activation or inactivation, wher...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1921
更新日期：2007-07-01 00:00:00
abstract：:Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are le...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-00733-0
更新日期：2021-01-01 00:00:00
abstract：:To determine the number of open Ca(2+) channels necessary for transmitter release at the inhibitory basket cell-granule cell synapse in rat hippocampus, we combined presynaptic Ca(2+) imaging, recording of postsynaptic currents and modeling. We found that that the opening of three or fewer Ca(2+) channels triggered tr...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2461
更新日期：2010-01-01 00:00:00
abstract：:Radial glial progenitor cells exhibit bidirectional cell cycle-dependent nuclear oscillations. The purpose and underlying mechanism of this unusual 'interkinetic nuclear migration' are poorly understood. We investigated the basis for this behavior by live imaging of nuclei, centrosomes and microtubules in embryonic ra...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2665
更新日期：2010-12-01 00:00:00
abstract：:High and low spatial frequency information in visual images is processed by distinct neural channels. Using event-related functional magnetic resonance imaging (fMRI) in humans, we show dissociable roles of such visual channels for processing faces and emotional fearful expressions. Neural responses in fusiform cortex...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1057
更新日期：2003-06-01 00:00:00
abstract：:Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes withi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-0621-y
更新日期：2020-06-01 00:00:00
abstract：:Axon degeneration is a hallmark of many neurodegenerative disorders. The current assumption is that the decision of injured axons to degenerate is cell-autonomously regulated. Here we show that Schwann cells (SCs), the glia of the peripheral nervous system, protect injured axons by virtue of a dramatic glycolytic upre...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-0689-4
更新日期：2020-10-01 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 neuroscience
pub_type： 已发布勘误
doi：10.1038/s41593-020-0595-9
更新日期：2020-02-01 00:00:00
abstract：:Neurobiological theories of knowledge processing are biased toward the language-dominant (usually the left) hemisphere. Does the right hemisphere critically contribute to knowledge processing? J.A. is a left-hemisphere language-dominant individual who suffered a lesion confined to the right mid- and anterior fusiform ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1721
更新日期：2006-07-01 00:00:00
abstract：:Laboratory models, including animal tissues and live animals, have proven useful for discovery of molecular targets of alcohol action as well as for characterization of genetic and environmental factors that influence alcohol's neural actions. Here we consider strengths and weaknesses of laboratory models used in alco...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn1581
更新日期：2005-11-01 00:00:00
abstract：:Autism spectrum disorder (ASD) is genetically heterogeneous with convergent symptomatology, suggesting common dysregulated pathways. In this study, we analyzed brain transcriptional changes in five mouse models of Pitt-Hopkins syndrome (PTHS), a syndromic form of ASD caused by mutations in the TCF4 gene, but not the T...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0578-x
更新日期：2020-03-01 00:00:00
abstract：:Endogenous cannabinoids (eCB) mediate synaptic plasticity in brain regions involved in learning and reward. Here we show that in mice, a single in-vivo exposure to Delta 9-tetrahydrocannabinol (THC) abolishes the retrograde signaling that underlies eCB-mediated synaptic plasticity in both nucleus accumbens (NAc) and h...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1251
更新日期：2004-06-01 00:00:00
abstract：:Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 ca...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0416-1
更新日期：2019-07-01 00:00:00
abstract：:Amyloid plaques are a hallmark of Alzheimer disease, but their importance in its pathogenesis is controversial. By neuronal labeling and transcranial two-photon imaging, we show in a transgenic mouse model of Alzheimer disease that dendrites passing through or near fibrillar amyloid deposits undergo spine loss and sha...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1335
更新日期：2004-11-01 00:00:00
abstract：:Long-term potentiation (LTP) is thought to be critically involved not only in learning and memory, but also during the activity-dependent developmental phases of neural circuit formation and refinement. Whether the mechanisms underlying LTP change during this phase of postnatal development, however, is unknown. We rep...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn985
更新日期：2003-01-01 00:00:00
abstract：:We elucidated the intrinsic circuitry of the medial prefrontal cortex and its role in regulating fear extinction, using neuronal tracing and optogenetic stimulation in vitro and in vivo. We show that pyramidal neurons in layer 5/6 of the prelimbic medial prefrontal cortex project to pyramidal cells in layer 5/6 of the...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0137-x
更新日期：2018-05-01 00:00:00
abstract：:The most critical attribute of human language is its unbounded combinatorial nature: smaller elements can be combined into larger structures on the basis of a grammatical system, resulting in a hierarchy of linguistic units, such as words, phrases and sentences. Mentally parsing and representing such structures, howev...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4186
更新日期：2016-01-01 00:00:00
abstract：:Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, litt...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2151
更新日期：2008-08-01 00:00:00
abstract：:Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm3 volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4576
更新日期：2017-07-01 00:00:00
abstract：:Understanding a sensory system implies the ability to predict responses to a variety of inputs from a common model. In the retina, this includes predicting how the integration of signals across visual space shapes the outputs of retinal ganglion cells. Existing models of this process generalize poorly to predict respo...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3225
更新日期：2012-11-01 00:00:00
abstract：:The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic in...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1933
更新日期：2007-08-01 00:00:00
abstract：:A hallmark of addiction is the loss of control over drug intake, which is seen in only a fraction of those exposed to stimulant drugs such as cocaine. The cellular mechanisms underlying vulnerability or resistance to compulsive drug use remain unknown. We found that individual variability in the development of highly ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3369
更新日期：2013-05-01 00:00:00
abstract：:The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associat...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4388
更新日期：2016-12-01 00:00:00
