当前位置： SCI文献检索 > Science Signaling期刊下所有文献 > Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.

Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.

Abstract：

:CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanism of suppression remains unclear. Here, we showed that human T(regs) rapidly suppressed the release of calcium ions (Ca(2+)) from intracellular stores in response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+) signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor κB (NF-κB). In contrast, Ca(2+)-independent events in T(cons), such as TCR-proximal signaling and activation of the transcription factor activator protein 1 (AP-1), were not affected during coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization, coculture with T(regs) did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the activity of NFAT and NF-κB and of the expression of the gene encoding the cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid mechanism of T(reg)-mediated suppression. This increased understanding of T(reg) function may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer.

journal_name

Sci Signal

journal_title

Science signaling

authors

Schmidt A,Oberle N,Weiss EM,Vobis D,Frischbutter S,Baumgrass R,Falk CS,Haag M,Brügger B,Lin H,Mayr GW,Reichardt P,Gunzer M,Suri-Payer E,Krammer PH

doi

10.1126/scisignal.2002179

subject

Has Abstract

pub_date

2011-12-20 00:00:00

pages

ra90

issue

204

eissn

1945-0877

issn

1937-9145

pii

4/204/ra90

journal_volume

4

pub_type

杂志文章

相关文献

Science Signaling文献大全
  • Bacterial invaders drive CRC progression.

    abstract：:The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al show that CRC cell-resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients. ...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.abc4218

    authors： Meyerson M

    更新日期：2020-08-11 00:00:00

  • A sweet spot in the FGFR signal transduction pathway.

    abstract：:The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2002789

    authors： Ghabrial AS

    更新日期：2012-01-17 00:00:00

  • Tumor suppression by LKB1: SIK-ness prevents metastasis.

    abstract：:The LKB1 serine-threonine kinase is a tumor suppressor that is inactivated in a large number of sporadic human lung non-small cell carcinomas (NSCLCs) and cervical cancers. Genetic deletion of LKB1 in various mouse tissues results in tumorigenesis, and loss of LKB1 increases metastasis in a mouse model of NSCLC. LKB1 ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.286pe55

    authors： Shaw RJ

    更新日期：2009-09-01 00:00:00

  • New connections: New targets for fighting hepatic steatosis.

    abstract：:Insight into the signaling pathways that regulate de novo lipogenesis may lead to new treatments for hepatic steatosis. ...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.aam9988

    authors： Wong W

    更新日期：2017-02-21 00:00:00

  • Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.

    abstract：:Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaf6625

    authors： Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

    更新日期：2016-10-11 00:00:00

  • Grooming and growing with microglia.

    abstract：:Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.3147jc8

    authors： Antony JM

    更新日期：2010-11-09 00:00:00

  • Do pancreatic β cells "taste" nutrients to secrete insulin?

    abstract：:Insulin secretion from pancreatic β cells is controlled by nutrients, hormones, and neurotransmitters. Unlike the latter, which work through classic receptors, glucose and most other nutrients do not interact with membrane receptors but must be metabolized by β cells to induce insulin secretion. Studies have revealed ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2003325

    authors： Henquin JC

    更新日期：2012-08-28 00:00:00

  • LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of Gα(s).

    abstract：:Ligand binding to certain heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) stimulates the rapid synthesis of cyclic adenosine monophosphate (cAMP) through the G protein α(s) subunit, which activates adenylyl cyclase (AC). We found that the transmembrane receptor low-density lipop...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2001464

    authors： Wan M,Li J,Herbst K,Zhang J,Yu B,Wu X,Qiu T,Lei W,Lindvall C,Williams BO,Ma H,Zhang F,Cao X

    更新日期：2011-03-15 00:00:00

  • Transglutaminase-catalyzed protein-protein cross-linking suppresses the activity of the NF-κB-like transcription factor relish.

    abstract：:Cross-linking of proteins by mammalian transglutaminases (TGs) plays important roles in physiological phenomena such as blood coagulation and skin formation. We show that Drosophila TG suppressed innate immune signaling in the gut. RNA interference (RNAi) directed against TG reduced the life span of flies reared under...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2003970

    authors： Shibata T,Sekihara S,Fujikawa T,Miyaji R,Maki K,Ishihara T,Koshiba T,Kawabata S

    更新日期：2013-07-23 00:00:00

  • Measurement of phosphorylated extracellular signal-regulated kinase 1 and 2 in an undergraduate teaching laboratory with ALPHAscreen technology.

    abstract：:Teaching the practical aspects of signal transduction to large undergraduate classes can be challenging when there is only a finite time frame in which to engage in laboratory activities. This teaching resource describes the use of bead-based ALPHAscreen technology for a class of 300 second-year biochemistry students,...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.262tr1

    authors： Hay DL

    更新日期：2009-03-17 00:00:00

  • Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its oncogenic potential.

    abstract：:The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aav2449

    authors： Bandekar SJ,Arang N,Tully ES,Tang BA,Barton BL,Li S,Gutkind JS,Tesmer JJG

    更新日期：2019-02-19 00:00:00

  • TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.

    abstract：:TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intrace...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2000278

    authors： Lange I,Yamamoto S,Partida-Sanchez S,Mori Y,Fleig A,Penner R

    更新日期：2009-05-19 00:00:00

  • De novo organ formation from differentiated cells: root nodule organogenesis.

    abstract：:The symbiotic interaction between Rhizobium bacteria and legume plants leads to the induction of a new developmental program: the formation of nitrogen-fixing root nodules. Nodulation is triggered by specific bacterial signals, the Nod factors, and integrates plant developmental regulatory pathways to reactivate diffe...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.149re11

    authors： Crespi M,Frugier F

    更新日期：2008-12-09 00:00:00

  • MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.

    abstract：:The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aan3286

    authors： Sandí MJ,Marshall CB,Balan M,Coyaud É,Zhou M,Monson DM,Ishiyama N,Chandrakumar AA,La Rose J,Couzens AL,Gingras AC,Raught B,Xu W,Ikura M,Morrison DK,Rottapel R

    更新日期：2017-10-31 00:00:00

  • TGF-β promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85α.

    abstract：:Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-β are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aal4186

    authors： Hamidi A,Song J,Thakur N,Itoh S,Marcusson A,Bergh A,Heldin CH,Landström M

    更新日期：2017-07-04 00:00:00

  • The STING in the tail for cytosolic DNA-dependent activation of IRF3.

    abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2002919

    authors： Bowie A

    更新日期：2012-03-06 00:00:00

  • Tumors block pain with CXCL12.

    abstract：:The chemokine CXCL12 released from early stage pancreatic cancer recruits Schwann cells and suppresses pain signaling. ...

    journal_title：Science signaling

    pub_type： 评论,杂志文章

    doi：10.1126/scisignal.aam7233

    authors： Gough NR

    更新日期：2017-01-10 00:00:00

  • Costimulatory role of CXCR4 with pre-TCR and its crosstalk with PI3K in beta-selection of thymocytes.

    abstract：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.3119jc4

    authors： Ahamed JA,Madhivadhani P

    更新日期：2010-04-27 00:00:00

  • Regulation of type I interferon: It's HIP to be K2.

    abstract：:Uncontrolled expression of type I interferon (IFN-I) drives autoimmunity, necessitating the need for tight regulation. In this issue, Cao et al reveal a role for the kinase HIPK2 in the transcriptional control of IFN-I during antiviral immune responses. ...

    journal_title：Science signaling

    pub_type： 评论,杂志文章,评审

    doi：10.1126/scisignal.aaw8549

    authors： Best SM,Ponia SS

    更新日期：2019-03-19 00:00:00

  • IRE1 prevents endoplasmic reticulum membrane permeabilization and cell death under pathological conditions.

    abstract：:The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IR...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaa0341

    authors： Kanekura K,Ma X,Murphy JT,Zhu LJ,Diwan A,Urano F

    更新日期：2015-06-23 00:00:00

  • Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.

    abstract：:Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aax0715

    authors： Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

    更新日期：2019-12-03 00:00:00

  • Itk controls the spatiotemporal organization of T cell activation.

    abstract：:During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2001821

    authors： Singleton KL,Gosh M,Dandekar RD,Au-Yeung BB,Ksionda O,Tybulewicz VL,Altman A,Fowell DJ,Wülfing C

    更新日期：2011-10-04 00:00:00

  • Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2).

    abstract：:Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aat9773

    authors： Cocco E,Javier Carmona F,Razavi P,Won HH,Cai Y,Rossi V,Chan C,Cownie J,Soong J,Toska E,Shifman SG,Sarotto I,Savas P,Wick MJ,Papadopoulos KP,Moriarty A,Cutler RE Jr,Avogadri-Connors F,Lalani AS,Bryce RP,Chandarlapa

    更新日期：2018-10-09 00:00:00

  • The chemokine CXCL12 generates costimulatory signals in T cells to enhance phosphorylation and clustering of the adaptor protein SLP-76.

    abstract：:The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2004018

    authors： Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

    更新日期：2013-07-30 00:00:00

  • Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

    abstract：:The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteo...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2004088

    authors： Gao J,Aksoy BA,Dogrusoz U,Dresdner G,Gross B,Sumer SO,Sun Y,Jacobsen A,Sinha R,Larsson E,Cerami E,Sander C,Schultz N

    更新日期：2013-04-02 00:00:00

  • Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.

    abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinas...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2005700

    authors： So J,Pasculescu A,Dai AY,Williton K,James A,Nguyen V,Creixell P,Schoof EM,Sinclair J,Barrios-Rodiles M,Gu J,Krizus A,Williams R,Olhovsky M,Dennis JW,Wrana JL,Linding R,Jorgensen C,Pawson T,Colwill K

    更新日期：2015-04-07 00:00:00

  • Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization.

    abstract：:The deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation o...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaa0441

    authors： Herhaus L,Perez-Oliva AB,Cozza G,Gourlay R,Weidlich S,Campbell DG,Pinna LA,Sapkota GP

    更新日期：2015-04-14 00:00:00

  • Sorting out memory and learning.

    abstract：:Mutations in AMPA receptor recycling machinery underlie cognitive impairment in an intellectual disorder and in neurodegenerative diseases. ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aan5454

    authors： Ferrarelli LK

    更新日期：2017-05-02 00:00:00

  • Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation.

    abstract：:Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaz0240

    authors： Sloutsky R,Dziedzic N,Dunn MJ,Bates RM,Torres-Ocampo AP,Boopathy S,Page B,Weeks JG,Chao LH,Stratton MM

    更新日期：2020-07-21 00:00:00

  • Full focus on calcium.

    abstract：:Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...

    journal_title：Science signaling

    pub_type：

    doi：10.1126/scisignal.aaz0961

    authors： Parys JB,Guse AH

    更新日期：2019-09-17 00:00:00