Asymmetric redundancy in CD4 silencer function.


:We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development. In this report, we use biochemical techniques to identify three different factor-binding sites within the CD4 silencer, denoted sites I, II, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone, or the combination of sites I and III permits silencer function. Thus, our data indicate that the mechanism of function of the CD4 silencer is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a factor binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.






Duncan DD,Adlam M,Siu G




Has Abstract


1996-03-01 00:00:00
















  • Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1α-Mediated Inflammatory Disease.

    abstract::Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6spin mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6spin mice....


    pub_type: 杂志文章


    authors: Gurung P,Fan G,Lukens JR,Vogel P,Tonks NK,Kanneganti TD

    更新日期:2017-04-18 00:00:00

  • Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.

    abstract::Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, w...


    pub_type: 杂志文章


    authors: Kawalekar OU,O'Connor RS,Fraietta JA,Guo L,McGettigan SE,Posey AD Jr,Patel PR,Guedan S,Scholler J,Keith B,Snyder NW,Blair IA,Milone MC,June CH

    更新日期:2016-02-16 00:00:00

  • CD5 Binds to Interleukin-6 and Induces a Feed-Forward Loop with the Transcription Factor STAT3 in B Cells to Promote Cancer.

    abstract::The participation of a specific subset of B cells and how they are regulated in cancer is unclear. Here, we demonstrate that the proportion of CD5(+) relative to interleukin-6 receptor α (IL-6Rα)-expressing B cells was greatly increased in tumors. CD5(+) B cells responded to IL-6 in the absence of IL-6Rα. IL-6 directl...


    pub_type: 杂志文章


    authors: Zhang C,Xin H,Zhang W,Yazaki PJ,Zhang Z,Le K,Li W,Lee H,Kwak L,Forman S,Jove R,Yu H

    更新日期:2016-04-19 00:00:00

  • Genome-wide Screens Identify Lineage- and Tumor-Specific Genes Modulating MHC-I- and MHC-II-Restricted Immunosurveillance of Human Lymphomas.

    abstract::Tumors frequently subvert major histocompatibility complex class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance, though how this is accomplished is not always well defined. To identify the global regulatory networks controlling antigen presentation, we employed genome-wide screening in human di...


    pub_type: 杂志文章


    authors: Dersh D,Phelan JD,Gumina ME,Wang B,Arbuckle JH,Holly J,Kishton RJ,Markowitz TE,Seedhom MO,Fridlyand N,Wright GW,Huang DW,Ceribelli M,Thomas CJ,Lack JB,Restifo NP,Kristie TM,Staudt LM,Yewdell JW

    更新日期:2021-01-12 00:00:00

  • Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals.

    abstract::The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefo...


    pub_type: 杂志文章


    authors: Ni L,Ye F,Cheng ML,Feng Y,Deng YQ,Zhao H,Wei P,Ge J,Gou M,Li X,Sun L,Cao T,Wang P,Zhou C,Zhang R,Liang P,Guo H,Wang X,Qin CF,Chen F,Dong C

    更新日期:2020-06-16 00:00:00

  • Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.

    abstract::Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed ...


    pub_type: 杂志文章


    authors: Joshi NS,Akama-Garren EH,Lu Y,Lee DY,Chang GP,Li A,DuPage M,Tammela T,Kerper NR,Farago AF,Robbins R,Crowley DM,Bronson RT,Jacks T

    更新日期:2015-09-15 00:00:00

  • Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells.

    abstract::Fever, an evolutionarily conserved physiological response to infection, is also commonly associated with many autoimmune diseases, but its role in T cell differentiation and autoimmunity remains largely unclear. T helper 17 (Th17) cells are critical in host defense and autoinflammatory diseases, with distinct phenotyp...


    pub_type: 杂志文章


    authors: Wang X,Ni L,Wan S,Zhao X,Ding X,Dejean A,Dong C

    更新日期:2020-02-18 00:00:00

  • A Shocking Type of Communication.

    abstract::In allergic patients, small amounts of allergen activate mast cells and trigger an immune cascade that can result in anaphylactic shock. In a recent issue of Science, Choi et al. (2018) show that dendritic cells sample the lumen of blood vessels and use microvesicles to trigger mast cell degranulation and anaphylaxis....


    pub_type: 评论,杂志文章


    authors: Sallis BF,Fiebiger E

    更新日期:2018-12-18 00:00:00

  • T cell-derived protein S engages TAM receptor signaling in dendritic cells to control the magnitude of the immune response.

    abstract::Dendritic cell (DC) activation is essential for the induction of immune defense against pathogens, yet needs to be tightly controlled to avoid chronic inflammation and exaggerated immune responses. Here, we identify a mechanism of immune homeostasis by which adaptive immunity, once triggered, tempers DC activation and...


    pub_type: 杂志文章


    authors: Carrera Silva EA,Chan PY,Joannas L,Errasti AE,Gagliani N,Bosurgi L,Jabbour M,Perry A,Smith-Chakmakova F,Mucida D,Cheroutre H,Burstyn-Cohen T,Leighton JA,Lemke G,Ghosh S,Rothlin CV

    更新日期:2013-07-25 00:00:00

  • Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells.

    abstract::Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyro...


    pub_type: 杂志文章


    authors: Bunin A,Sisirak V,Ghosh HS,Grajkowska LT,Hou ZE,Miron M,Yang C,Ceribelli M,Uetani N,Chaperot L,Plumas J,Hendriks W,Tremblay ML,Häcker H,Staudt LM,Green PH,Bhagat G,Reizis B

    更新日期:2015-08-18 00:00:00

  • microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells.

    abstract::microRNA-155 (miR-155) is expressed by cells of the immune system after activation and has been shown to be required for antibody production after vaccination with attenuated Salmonella. Here we show the intrinsic requirement for miR-155 in B cell responses to thymus-dependent and -independent antigens. B cells lackin...


    pub_type: 杂志文章


    authors: Vigorito E,Perks KL,Abreu-Goodger C,Bunting S,Xiang Z,Kohlhaas S,Das PP,Miska EA,Rodriguez A,Bradley A,Smith KG,Rada C,Enright AJ,Toellner KM,Maclennan IC,Turner M

    更新日期:2007-12-01 00:00:00

  • T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate.

    abstract::Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6loCD69hi expressing a transcription factor IRF4 and higher-affinit...


    pub_type: 杂志文章


    authors: Ise W,Fujii K,Shiroguchi K,Ito A,Kometani K,Takeda K,Kawakami E,Yamashita K,Suzuki K,Okada T,Kurosaki T

    更新日期:2018-04-17 00:00:00

  • Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84.

    abstract::CD4(+) T cells deficient in signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) exhibit a selective impairment in adhesion to antigen-presenting B cells but not dendritic cells (DCs), resulting in defective germinal center formation. However, the nature of this selective adhesion defect remained u...


    pub_type: 杂志文章


    authors: Cannons JL,Qi H,Lu KT,Dutta M,Gomez-Rodriguez J,Cheng J,Wakeland EK,Germain RN,Schwartzberg PL

    更新日期:2010-02-26 00:00:00

  • Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL.

    abstract::T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/d...


    pub_type: 杂志文章


    authors: Speir JA,Abdel-Motal UM,Jondal M,Wilson IA

    更新日期:1999-01-01 00:00:00

  • Regulatory B cells: origin, phenotype, and function.

    abstract::Regulatory B (Breg) cells are immunosuppressive cells that support immunological tolerance. Through the production of interleukin-10 (IL-10), IL-35, and transforming growth factor β (TGF-β), Breg cells suppress immunopathology by prohibiting the expansion of pathogenic T cells and other pro-inflammatory lymphocytes. R...


    pub_type: 杂志文章,评审


    authors: Rosser EC,Mauri C

    更新日期:2015-04-21 00:00:00

  • T cell receptor beta chain gene rearrangement and selection during thymocyte development in adult mice.

    abstract::The identification is made in normal mice of the stages in T cell development at which the rearranged beta chain of the T cell receptor (TCR) is utilized to promote T cell maturation, independent of the TCR alpha chain. In addition, evidence is provided that utilization of beta chains in T cell progenitors does not pr...


    pub_type: 杂志文章


    authors: Dudley EC,Petrie HT,Shah LM,Owen MJ,Hayday AC

    更新日期:1994-05-01 00:00:00

  • Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme.

    abstract::Members of the extended interleukin-1 (IL-1) cytokine family, such as IL-1, IL-18, IL-33, and IL-36, play a pivotal role in the initiation and amplification of immune responses. However, deregulated production and/or activation of these cytokines can lead to the development of multiple inflammatory disorders. IL-1 fam...


    pub_type: 杂志文章,评审


    authors: Afonina IS,Müller C,Martin SJ,Beyaert R

    更新日期:2015-06-16 00:00:00

  • Class-Switch Recombination Occurs Infrequently in Germinal Centers.

    abstract::Class-switch recombination (CSR) is a DNA recombination process that replaces the immunoglobulin (Ig) constant region for the isotype that can best protect against the pathogen. Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding the timing and location of CSR is therefore important. ...


    pub_type: 杂志文章


    authors: Roco JA,Mesin L,Binder SC,Nefzger C,Gonzalez-Figueroa P,Canete PF,Ellyard J,Shen Q,Robert PA,Cappello J,Vohra H,Zhang Y,Nowosad CR,Schiepers A,Corcoran LM,Toellner KM,Polo JM,Meyer-Hermann M,Victora GD,Vinuesa CG

    更新日期:2019-08-20 00:00:00

  • CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells.

    abstract::The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8+ TILs ha...


    pub_type: 杂志文章


    authors: Braun M,Aguilera AR,Sundarrajan A,Corvino D,Stannard K,Krumeich S,Das I,Lima LG,Meza Guzman LG,Li K,Li R,Salim N,Jorge MV,Ham S,Kelly G,Vari F,Lepletier A,Raghavendra A,Pearson S,Madore J,Jacquelin S,Effern M,

    更新日期:2020-10-13 00:00:00

  • A RHIM with a View: FLYing with Functional Amyloids.

    abstract::Recognition of bacterial peptidoglycan by the Drosophila IMD pathway triggers NF-κB activation and an associated immune response. In this issue of Immunity, Kleino et al. (2017) show that proteins in the IMD pathway form functional amyloids via a cryptic motif resembling the RHIM motif found in mammalian RIPK proteins...


    pub_type: 评论,杂志文章


    authors: Shin S,Cherry S

    更新日期:2017-10-17 00:00:00

  • Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy.

    abstract::The NF-κB pathway plays a crucial role in supporting tumor initiation, progression, and radioresistance of tumor cells. However, the role of the NF-κB pathway in radiation-induced anti-tumor host immunity remains unclear. Here we demonstrated that inhibiting the canonical NF-κB pathway dampened the therapeutic effect ...


    pub_type: 杂志文章


    authors: Hou Y,Liang H,Rao E,Zheng W,Huang X,Deng L,Zhang Y,Yu X,Xu M,Mauceri H,Arina A,Weichselbaum RR,Fu YX

    更新日期:2018-09-18 00:00:00

  • Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.

    abstract::CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating alpha galactosylceramide (alphaGalCer) analogs that give pr...


    pub_type: 杂志文章


    authors: Im JS,Arora P,Bricard G,Molano A,Venkataswamy MM,Baine I,Jerud ES,Goldberg MF,Baena A,Yu KO,Ndonye RM,Howell AR,Yuan W,Cresswell P,Chang YT,Illarionov PA,Besra GS,Porcelli SA

    更新日期:2009-06-19 00:00:00

  • MicroRNAs prevent the generation of autoreactive antibodies.

    abstract::MicroRNAs have been shown to be critical for a number of aspects of immune system regulation and function. Here, we have examined the role of microRNAs in terminal B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice. We found that in the absence of Dicer, the transitional and marginal zone (MZ) B cel...


    pub_type: 杂志文章


    authors: Belver L,de Yébenes VG,Ramiro AR

    更新日期:2010-11-24 00:00:00

  • Regulatory T cell lineage specification by the forkhead transcription factor foxp3.

    abstract::Regulatory T cell-mediated dominant tolerance has been demonstrated to play an important role in the prevention of autoimmunity. Here, we present data arguing that the forkhead transcription factor Foxp3 acts as the regulatory T cell lineage specification factor and mediator of the genetic mechanism of dominant tolera...


    pub_type: 杂志文章


    authors: Fontenot JD,Rasmussen JP,Williams LM,Dooley JL,Farr AG,Rudensky AY

    更新日期:2005-03-01 00:00:00

  • Caspase activation by granzyme B is indirect, and caspase autoprocessing requires the release of proapoptotic mitochondrial factors.

    abstract::Apoptosis in response to granzyme B involves activation of caspase-dependent target cell death pathways. Herein, we show that granzyme B initiates caspase processing but cannot fully process procaspase-3 in intact Jurkat T leukemia or NT2 neuronal cells. Rather, the release from mitochondria of proapoptotic mediators ...


    pub_type: 杂志文章


    authors: Sutton VR,Wowk ME,Cancilla M,Trapani JA

    更新日期:2003-03-01 00:00:00

  • Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis.

    abstract::The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127- and CD127+ early lymp...


    pub_type: 杂志文章


    authors: Alhaj Hussen K,Vu Manh TP,Guimiot F,Nelson E,Chabaane E,Delord M,Barbier M,Berthault C,Dulphy N,Alberdi AJ,Burlen-Defranoux O,Socié G,Bories JC,Larghero J,Vanneaux V,Verhoeyen E,Wirth T,Dalod M,Gluckman JC,Cumano A

    更新日期:2017-10-17 00:00:00

  • Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.

    abstract::Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene enc...


    pub_type: 杂志文章


    authors: Hughes PD,Belz GT,Fortner KA,Budd RC,Strasser A,Bouillet P

    更新日期:2008-02-01 00:00:00

  • The structure of a Bcl-xL/Bim fragment complex: implications for Bim function.

    abstract::After antigen-driven expansion, the majority of T cells involved in an immune response die rapidly by apoptosis dependent on the Bcl-2 related proteins, Bim and Bax or Bak. The details of how these proteins are activated and interact are still unclear. The crystal structure of mouse Bcl-x(L) bound to a long helical fr...


    pub_type: 杂志文章


    authors: Liu X,Dai S,Zhu Y,Marrack P,Kappler JW

    更新日期:2003-09-01 00:00:00

  • Asymmetric processing of coding ends and the effect of coding end nucleotide composition on V(D)J recombination.

    abstract::The products of V(D)J recombination are coding and signal joints. We show that the nucleotide composition of the coding ends affects V(D)J recombination. The presence of Ts at the 5' end of either the 12 mer or the 23 mer recombination signal sequence (RSS) greatly decreases coding and signal joint formation, and Ts a...


    pub_type: 杂志文章


    authors: Ezekiel UR,Engler P,Stern D,Storb U

    更新日期:1995-04-01 00:00:00

  • Widespread immunological functions of mast cells: fact or fiction?

    abstract::Immunological functions of mast cells are currently considered to be much broader than the original role of mast cells in IgE-driven allergic disease. The spectrum of proposed mast cell functions includes areas as diverse as the regulation of innate and adaptive immune responses, protective immunity against viral, mic...


    pub_type: 杂志文章,评审


    authors: Rodewald HR,Feyerabend TB

    更新日期:2012-07-27 00:00:00