An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.

Abstract:

:The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream' inhibitory signaling. Consequently, the cytotoxicity of NK cells was higher in beta-arrestin 2-deficient mice but was inhibited in beta-arrestin 2-transgenic mice. Moreover, beta-arrestin 2-deficient mice were less susceptible than wild-type mice to mouse cytomegalovirus infection, an effect that was abolished by depletion of NK cells. Our findings identify a previously unknown mechanism by which the inhibitory signaling in NK cells is regulated.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Yu MC,Su LL,Zou L,Liu Y,Wu N,Kong L,Zhuang ZH,Sun L,Liu HP,Hu JH,Li D,Strominger JL,Zang JW,Pei G,Ge BX

doi

10.1038/ni.1635

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

898-907

issue

8

eissn

1529-2908

issn

1529-2916

pii

ni.1635

journal_volume

9

pub_type

杂志文章
  • T cells use two directionally distinct pathways for cytokine secretion.

    abstract::Activated T helper cells produce many cytokines, some of which are secreted through the immunological synapse toward the antigen-presenting cell. Here we have used immunocytochemistry, live-cell imaging and a surface-mediated secretion assay to show that there are two cytokine export pathways in T helper cells. Some c...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1304

    authors: Huse M,Lillemeier BF,Kuhns MS,Chen DS,Davis MM

    更新日期:2006-03-01 00:00:00

  • Genetic variation in Toll-like receptors and disease susceptibility.

    abstract::Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2284

    authors: Netea MG,Wijmenga C,O'Neill LA

    更新日期:2012-05-18 00:00:00

  • CCR5 provides a signal for microbial induced production of IL-12 by CD8 alpha+ dendritic cells.

    abstract::The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens. Here we show that ligation of the C-C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8 alpha+...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/76957

    authors: Aliberti J,Reis e Sousa C,Schito M,Hieny S,Wells T,Huffnagle GB,Sher A

    更新日期:2000-07-01 00:00:00

  • Structural mechanisms of costimulation.

    abstract::Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni0502-427

    authors: Schwartz JC,Zhang X,Nathenson SG,Almo SC

    更新日期:2002-05-01 00:00:00

  • The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling.

    abstract::The actin cytoskeleton seems to play two critical roles in the activation of T cells. One of these roles is T cell shape development and movement, including formation of the immunological synapse. The other is the formation of a scaffold for signaling components. This review focuses on the recent convergence of cell b...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/76877

    authors: Dustin ML,Cooper JA

    更新日期:2000-07-01 00:00:00

  • A suspenseful game of 'hide and seek' between virus and host.

    abstract::As part of the most important contributions to the understanding of viral immunity, Michael Oldstone recounts his pioneering work on lymphocytic choriomeningitis virus. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni0407-325

    authors: Oldstone MB

    更新日期:2007-04-01 00:00:00

  • The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses.

    abstract::Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2541

    authors: Bell BD,Kitajima M,Larson RP,Stoklasek TA,Dang K,Sakamoto K,Wagner KU,Kaplan DH,Reizis B,Hennighausen L,Ziegler SF

    更新日期:2013-04-01 00:00:00

  • NF-κB-mediated degradation of the coactivator RIP140 regulates inflammatory responses and contributes to endotoxin tolerance.

    abstract::Tolerance to endotoxins that is triggered by prior exposure to Toll-like receptor (TLR) ligands provides a mechanism with which to dampen inflammatory cytokines. The receptor-interacting protein RIP140 interacts with the transcription factor NF-κB to regulate the expression of genes encoding proinflammatory cytokines....

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2238

    authors: Ho PC,Tsui YC,Feng X,Greaves DR,Wei LN

    更新日期:2012-03-04 00:00:00

  • Tissue-resident macrophages.

    abstract::Tissue-resident macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These range from dedicated homeostatic functions, such as clearance of cellular debris and iron processing, to central roles in tissue immune surveillance, response to infection and the...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2705

    authors: Davies LC,Jenkins SJ,Allen JE,Taylor PR

    更新日期:2013-10-01 00:00:00

  • Production of Ins(1,3,4,5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation.

    abstract::Antigen receptor-mediated production of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in lymphocytes triggers the release of Ca2+ from intracellular stores; this release of Ca2+ results in the opening of store-operated Ca2+ channels in the plasma membrane. Here we report that mice lacking Ins(1,4,5)P3 3-kinase B (Itpkb)...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1458

    authors: Miller AT,Sandberg M,Huang YH,Young M,Sutton S,Sauer K,Cooke MP

    更新日期:2007-05-01 00:00:00

  • Publisher Correction: Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes.

    abstract::In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Suppl...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-018-0154-7

    authors: Zhang M,Dong Y,Hu F,Yang D,Zhao Q,Lv C,Wang Y,Xia C,Weng Q,Liu X,Li C,Zhou P,Wang T,Guan Y,Guo R,Liu L,Geng Y,Wu H,Du J,Hu Z,Xu S,Chen J,He A,Liu B,Wang D,Yang YG,Wang J

    更新日期:2018-09-01 00:00:00

  • New insights into the multidimensional concept of macrophage ontogeny, activation and function.

    abstract::Macrophages have protective roles in immunity to pathogens, tissue development, homeostasis and repair following damage. Maladaptive immunity and inflammation provoke changes in macrophage function that are causative of disease. Despite a historical wealth of knowledge about macrophages, recent advances have revealed ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3324

    authors: Ginhoux F,Schultze JL,Murray PJ,Ochando J,Biswas SK

    更新日期:2016-01-01 00:00:00

  • Autophagy and autophagy-related proteins in the immune system.

    abstract::Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In add...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.3273

    authors: Shibutani ST,Saitoh T,Nowag H,Münz C,Yoshimori T

    更新日期:2015-10-01 00:00:00

  • Programming dendritic cells to induce T(H)2 and tolerogenic responses.

    abstract::A fundamental puzzle in immunology is how the immune system decides what types of immune responses to launch against different stimuli. Although much is known about control of T helper type 1 (T(H)1) and T(H)17 responses, the mechanisms that initiate T(H)2 and T regulatory (T(reg)) responses remain obscure. Emerging s...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.1894

    authors: Pulendran B,Tang H,Manicassamy S

    更新日期:2010-08-01 00:00:00

  • Post-transcriptional coordination of immunological responses by RNA-binding proteins.

    abstract::Immunological reactions are propelled by ever-changing signals that alter the translational ability of the RNA in the cells involved. Such alterations are considered to be consequential modifications in the transcriptomic decoding of the genetic blueprint. The identification of RNA-binding protein (RBP) assemblies eng...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2884

    authors: Kafasla P,Skliris A,Kontoyiannis DL

    更新日期:2014-06-01 00:00:00

  • Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm.

    abstract::Plasticity is a hallmark of cells of the myelomonocytic lineage. In response to innate recognition or signals from lymphocyte subsets, mononuclear phagocytes undergo adaptive responses. Shaping of monocyte-macrophage function is an essential component of resistance to pathogens, tissue damage and repair. The orchestra...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.1937

    authors: Biswas SK,Mantovani A

    更新日期:2010-10-01 00:00:00

  • Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.

    abstract::Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2180

    authors: Butler NS,Moebius J,Pewe LL,Traore B,Doumbo OK,Tygrett LT,Waldschmidt TJ,Crompton PD,Harty JT

    更新日期:2011-12-11 00:00:00

  • Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase.

    abstract::The variable lymphocyte receptors (VLRs) of jawless vertebrates such as lamprey and hagfish are composed of highly diverse modular leucine-rich repeats. Each lymphocyte assembles a unique VLR by rearrangement of the germline gene. In the lamprey genome, we identify here about 850 distinct cassettes encoding leucine-ri...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1463

    authors: Rogozin IB,Iyer LM,Liang L,Glazko GV,Liston VG,Pavlov YI,Aravind L,Pancer Z

    更新日期:2007-06-01 00:00:00

  • Apoptosis in the development and maintenance of the immune system.

    abstract::Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death dom...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni0503-410

    authors: Opferman JT,Korsmeyer SJ

    更新日期:2003-05-01 00:00:00

  • IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor.

    abstract::CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue t...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-00850-9

    authors: Liu Y,Zhou N,Zhou L,Wang J,Zhou Y,Zhang T,Fang Y,Deng J,Gao Y,Liang X,Lv J,Wang Z,Xie J,Xue Y,Zhang H,Ma J,Tang K,Fang Y,Cheng F,Zhang C,Dong B,Zhao Y,Yuan P,Gao Q,Zhang H,Xiao-Feng Qin F,Huang B

    更新日期:2021-01-11 00:00:00

  • Different molecular complexes that mediate transcriptional induction and repression by FoxP3.

    abstract::FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3835

    authors: Kwon HK,Chen HM,Mathis D,Benoist C

    更新日期:2017-11-01 00:00:00

  • A Toll-like receptor 2-integrin beta3 complex senses bacterial lipopeptides via vitronectin.

    abstract::Toll-like receptor 2 (TLR2) initiates inflammation in response to bacterial lipopeptide (BLP). However, the molecular mechanisms enabling the detection of BLP by TLR2 are unknown. Here we investigated the interaction of BLP with human serum proteins and identified vitronectin as a BLP-recognition molecule. Vitronectin...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1618

    authors: Gerold G,Abu Ajaj K,Bienert M,Laws HJ,Zychlinsky A,de Diego JL

    更新日期:2008-07-01 00:00:00

  • On regulation of phagosome maturation and antigen presentation.

    abstract::Phagocytosis has essential functions in immunity. Here we highlight the presence of a subcellular level of self-non-self discrimination in dendritic cells that operates at the level of individual phagosomes. We discuss how engagement of Toll-like receptor signaling controls distinct programs of phagosome maturation. A...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1006-1029

    authors: Blander JM,Medzhitov R

    更新日期:2006-10-01 00:00:00

  • Chd4 choreographs self-antigen expression for central immune tolerance.

    abstract::Autoreactive T cells are eliminated in the thymus to prevent autoimmunity by promiscuous expression of tissue-restricted self-antigens in medullary thymic epithelial cells. This expression is dependent on the transcription factor Fezf2, as well as the transcriptional regulator Aire, but the entire picture of the trans...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0717-2

    authors: Tomofuji Y,Takaba H,Suzuki HI,Benlaribi R,Martinez CDP,Abe Y,Morishita Y,Okamura T,Taguchi A,Kodama T,Takayanagi H

    更新日期:2020-08-01 00:00:00

  • Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.

    abstract::DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1204

    authors: Hamerman JA,Tchao NK,Lowell CA,Lanier LL

    更新日期:2005-06-01 00:00:00

  • Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease.

    abstract::Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell a...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2928

    authors: Miyazaki M,Miyazaki K,Chen S,Itoi M,Miller M,Lu LF,Varki N,Chang AN,Broide DH,Murre C

    更新日期:2014-08-01 00:00:00

  • TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

    abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0544-5

    authors: Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JC

    更新日期:2019-12-01 00:00:00

  • Analysis of regulatory CD8 T cells in Qa-1-deficient mice.

    abstract::The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1063

    authors: Hu D,Ikizawa K,Lu L,Sanchirico ME,Shinohara ML,Cantor H

    更新日期:2004-05-01 00:00:00

  • Hydrogen peroxide as second messenger in lymphocyte activation.

    abstract::Oxidants such as H2O2 are connected to lymphocyte activation, but the molecular mechanisms behind this phenomenon are less clear. Here, I review data suggesting that by inhibiting protein tyrosine phosphatases, H2O2 plays an important role as a secondary messenger in the initiation and amplification of signaling at th...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1202-1129

    authors: Reth M

    更新日期:2002-12-01 00:00:00

  • The nonimmunoglobulin portion of lambda5 mediates cell-autonomous pre-B cell receptor signaling.

    abstract::The pre-B cell receptor (preBCR), composed of mu immunoglobulin (Ig) and surrogate light chains, signals large 'preB-II' cells to proliferate in the apparent absence of ligands or cooperating cells. We deleted the N-terminal, nonimmunoglobulin (nonlg) portion of lambda5, or mutated seven arginine residues in it to ser...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni959

    authors: Ohnishi K,Melchers F

    更新日期:2003-09-01 00:00:00