当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity.

A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity.

Abstract：

:Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with leptomeningeal phagocytes. During established disease, the activation process is extended to the depth of the CNS parenchyma, where the cells form contacts with microglia and recruited phagocytes. We show that it is the activation processes during the preclinical phase rather than during established disease that are essential for the intensity and duration of the disease bout.

journal_name

Nat Med

journal_title

Nature medicine

authors

Lodygin D,Odoardi F,Schläger C,Körner H,Kitz A,Nosov M,van den Brandt J,Reichardt HM,Haberl M,Flügel A

doi

10.1038/nm.3182

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

784-90

issue

6

eissn

1078-8956

issn

1546-170X

pii

nm.3182

journal_volume

19

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia.

    abstract：:T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced ne...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1524

    authors： Vilimas T,Mascarenhas J,Palomero T,Mandal M,Buonamici S,Meng F,Thompson B,Spaulding C,Macaroun S,Alegre ML,Kee BL,Ferrando A,Miele L,Aifantis I

    更新日期：2007-01-01 00:00:00

  • Myocardial infarction accelerates breast cancer via innate immune reprogramming.

    abstract：:Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3-5. While eleva...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0964-7

    authors： Koelwyn GJ,Newman AAC,Afonso MS,van Solingen C,Corr EM,Brown EJ,Albers KB,Yamaguchi N,Narke D,Schlegel M,Sharma M,Shanley LC,Barrett TJ,Rahman K,Mezzano V,Fisher EA,Park DS,Newman JD,Quail DF,Nelson ER,Caan BJ,J

    更新日期：2020-09-01 00:00:00

  • Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis.

    abstract：:The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm859

    authors： Pym AS,Brodin P,Majlessi L,Brosch R,Demangel C,Williams A,Griffiths KE,Marchal G,Leclerc C,Cole ST

    更新日期：2003-05-01 00:00:00

  • Direct-to-stomach delivery.

    abstract：: ...

    journal_title：Nature medicine

    pub_type： 评论,杂志文章

    doi：10.1038/s41591-019-0397-3

    authors： Stower H

    更新日期：2019-03-01 00:00:00

  • IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.

    abstract：:Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining loc...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1710

    authors： Aujla SJ,Chan YR,Zheng M,Fei M,Askew DJ,Pociask DA,Reinhart TA,McAllister F,Edeal J,Gaus K,Husain S,Kreindler JL,Dubin PJ,Pilewski JM,Myerburg MM,Mason CA,Iwakura Y,Kolls JK

    更新日期：2008-03-01 00:00:00

  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

    abstract：:It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0457-8

    authors： Frésard L,Smail C,Ferraro NM,Teran NA,Li X,Smith KS,Bonner D,Kernohan KD,Marwaha S,Zappala Z,Balliu B,Davis JR,Liu B,Prybol CJ,Kohler JN,Zastrow DB,Reuter CM,Fisk DG,Grove ME,Davidson JM,Hartley T,Joshi R,Stro

    更新日期：2019-06-01 00:00:00

  • Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.

    abstract：:Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4421

    authors： Huot N,Jacquelin B,Garcia-Tellez T,Rascle P,Ploquin MJ,Madec Y,Reeves RK,Derreudre-Bosquet N,Müller-Trutwin M

    更新日期：2017-11-01 00:00:00

  • Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection.

    abstract：:Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (term...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1192

    authors： Morizono K,Xie Y,Ringpis GE,Johnson M,Nassanian H,Lee B,Wu L,Chen IS

    更新日期：2005-03-01 00:00:00

  • Developing neoantigen-targeted T cell-based treatments for solid tumors.

    abstract：:Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting 'neoantigens'-the somatic mutations expressed only by tumor cells-might...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-019-0596-y

    authors： Yamamoto TN,Kishton RJ,Restifo NP

    更新日期：2019-10-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract：:There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-018-0104-9

    authors： Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期：2018-07-01 00:00:00

  • Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain.

    abstract：:Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brai...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2749

    authors： Shichita T,Hasegawa E,Kimura A,Morita R,Sakaguchi R,Takada I,Sekiya T,Ooboshi H,Kitazono T,Yanagawa T,Ishii T,Takahashi H,Mori S,Nishibori M,Kuroda K,Akira S,Miyake K,Yoshimura A

    更新日期：2012-06-01 00:00:00

  • GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes.

    abstract：:GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1097-1096

    authors： Stenbit AE,Tsao TS,Li J,Burcelin R,Geenen DL,Factor SM,Houseknecht K,Katz EB,Charron MJ

    更新日期：1997-10-01 00:00:00

  • A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.

    abstract：:Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3665

    authors： Herranz D,Ambesi-Impiombato A,Palomero T,Schnell SA,Belver L,Wendorff AA,Xu L,Castillo-Martin M,Llobet-Navás D,Cordon-Cardo C,Clappier E,Soulier J,Ferrando AA

    更新日期：2014-10-01 00:00:00

  • Human lupus T cells resist inactivation and escape death by upregulating COX-2.

    abstract：:Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death recept...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1005

    authors： Xu L,Zhang L,Yi Y,Kang HK,Datta SK

    更新日期：2004-04-01 00:00:00

  • Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring.

    abstract：:In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep ta...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0915-3

    authors： Zviran A,Schulman RC,Shah M,Hill STK,Deochand S,Khamnei CC,Maloney D,Patel K,Liao W,Widman AJ,Wong P,Callahan MK,Ha G,Reed S,Rotem D,Frederick D,Sharova T,Miao B,Kim T,Gydush G,Rhoades J,Huang KY,Omans ND,Bo

    更新日期：2020-07-01 00:00:00

  • A new role for Nogo as a regulator of vascular remodeling.

    abstract：:Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cu...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1020

    authors： Acevedo L,Yu J,Erdjument-Bromage H,Miao RQ,Kim JE,Fulton D,Tempst P,Strittmatter SM,Sessa WC

    更新日期：2004-04-01 00:00:00

  • Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network.

    abstract：:Computerized electrocardiogram (ECG) interpretation plays a critical role in the clinical ECG workflow1. Widely available digital ECG data and the algorithmic paradigm of deep learning2 present an opportunity to substantially improve the accuracy and scalability of automated ECG analysis. However, a comprehensive eval...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0268-3

    authors： Hannun AY,Rajpurkar P,Haghpanahi M,Tison GH,Bourn C,Turakhia MP,Ng AY

    更新日期：2019-01-01 00:00:00

  • Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing.

    abstract：:With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived C...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4355

    authors： Crespo M,Vilar E,Tsai SY,Chang K,Amin S,Srinivasan T,Zhang T,Pipalia NH,Chen HJ,Witherspoon M,Gordillo M,Xiang JZ,Maxfield FR,Lipkin S,Evans T,Chen S

    更新日期：2017-07-01 00:00:00

  • Adding to the checkpoint blockade armamentarium.

    abstract：: ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0350-5

    authors： Hellmann MD,Snyder A

    更新日期：2019-02-01 00:00:00

  • A negative regulator of MAP kinase causes depressive behavior.

    abstract：:The lifetime prevalence (∼16%) and the economic burden ($100 billion annually) associated with major depressive disorder (MDD) make it one of the most common and debilitating neurobiological illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology of MDD have not been identified. ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2219

    authors： Duric V,Banasr M,Licznerski P,Schmidt HD,Stockmeier CA,Simen AA,Newton SS,Duman RS

    更新日期：2010-11-01 00:00:00

  • A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis.

    abstract：:Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAE...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0523-2

    authors： Johnson DB,McDonnell WJ,Gonzalez-Ericsson PI,Al-Rohil RN,Mobley BC,Salem JE,Wang DY,Sanchez V,Wang Y,Chastain CA,Barker K,Liang Y,Warren S,Beechem JM,Menzies AM,Tio M,Long GV,Cohen JV,Guidon AC,O'Hare M,Chandra S

    更新日期：2019-08-01 00:00:00

  • DNA repair processes are critical mediators of p53-dependent tumor suppression.

    abstract：:It has long been assumed that p53 suppresses tumor development through induction of apoptosis, possibly with contributions by cell cycle arrest and cell senescence1,2. However, combined deficiency in these three processes does not result in spontaneous tumor formation as observed upon loss of p53, suggesting the exist...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0043-5

    authors： Janic A,Valente LJ,Wakefield MJ,Di Stefano L,Milla L,Wilcox S,Yang H,Tai L,Vandenberg CJ,Kueh AJ,Mizutani S,Brennan MS,Schenk RL,Lindqvist LM,Papenfuss AT,O'Connor L,Strasser A,Herold MJ

    更新日期：2018-07-01 00:00:00

  • Cannabinoid CB1 receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior.

    abstract：:Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular m...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0299-9

    authors： Shen CJ,Zheng D,Li KX,Yang JM,Pan HQ,Yu XD,Fu JY,Zhu Y,Sun QX,Tang MY,Zhang Y,Sun P,Xie Y,Duan S,Hu H,Li XM

    更新日期：2019-02-01 00:00:00

  • The effects of tobacco control policies on global smoking prevalence.

    abstract：:Substantial global effort has been devoted to curtailing the tobacco epidemic over the past two decades, especially after the adoption of the Framework Convention on Tobacco Control1 by the World Health Organization in 2003. In 2015, in recognition of the burden resulting from tobacco use, strengthened tobacco control...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-01210-8

    authors： Flor LS,Reitsma MB,Gupta V,Ng M,Gakidou E

    更新日期：2021-01-21 00:00:00

  • Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans.

    abstract：:Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. T...

    journal_title：Nature medicine

    pub_type： 杂志文章,随机对照试验

    doi：10.1038/s41591-020-0801-z

    authors： Basolo A,Hohenadel M,Ang QY,Piaggi P,Heinitz S,Walter M,Walter P,Parrington S,Trinidad DD,von Schwartzenberg RJ,Turnbaugh PJ,Krakoff J

    更新日期：2020-04-01 00:00:00

  • In situ genetic analysis of cellular chimerism.

    abstract：:Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish betw...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1862

    authors： Wu D,Vu Q,Nguyen A,Stone JR,Stubbs H,Kuhlmann G,Sholl LM,Iafrate AJ

    更新日期：2009-02-01 00:00:00

  • Cancer's true breakthroughs.

    abstract：:A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estima...

    journal_title：Nature medicine

    pub_type： 新闻

    doi：10.1038/nm.3245

    authors： Dolgin E

    更新日期：2013-06-01 00:00:00

  • Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab.

    abstract：:Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung canc...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0134-3

    authors： Gandara DR,Paul SM,Kowanetz M,Schleifman E,Zou W,Li Y,Rittmeyer A,Fehrenbacher L,Otto G,Malboeuf C,Lieber DS,Lipson D,Silterra J,Amler L,Riehl T,Cummings CA,Hegde PS,Sandler A,Ballinger M,Fabrizio D,Mok T,Shames

    更新日期：2018-09-01 00:00:00

  • Sema3a maintains normal heart rhythm through sympathetic innervation patterning.

    abstract：:Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a,...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1570

    authors： Ieda M,Kanazawa H,Kimura K,Hattori F,Ieda Y,Taniguchi M,Lee JK,Matsumura K,Tomita Y,Miyoshi S,Shimoda K,Makino S,Sano M,Kodama I,Ogawa S,Fukuda K

    更新日期：2007-05-01 00:00:00

  • Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.

    abstract：:The androgen receptor (AR) is involved in the development, growth and progression of prostate cancer (CaP). CaP often progresses from an androgen-dependent to an androgen-independent tumor, making androgen ablation therapy ineffective. However, the mechanisms for the development of androgen-independent CaP are unclear...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/76287

    authors： Zhao XY,Malloy PJ,Krishnan AV,Swami S,Navone NM,Peehl DM,Feldman D

    更新日期：2000-06-01 00:00:00