Immunology articles within Nature

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  • Letter |

    Activation of inflammatory gene expression by toll-like receptor (TLR) signalling pathways involves the removal of gene repression complexes such as NCoR. Here, coronin 2A, a component of the NCoR complex, is shown to mediate TLR-induced NCoR turnover and de-repression of inflammatory genes by a mechanism involving interaction with oligomeric nuclear actin.

    • Wendy Huang
    • , Serena Ghisletti
    •  & Christopher K. Glass

  • Letter |

    A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here, 33 distinct enhancers within this region are identified, showing that SNPs in one of the enhancers affect STAT1 binding. Furthermore, it is shown that in human vascular endothelial cells the enhancer interval physically interacts with a number of specific loci and that IFN-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.

    • Olivier Harismendy
    • , Dimple Notani
    •  & Kelly A. Frazer

  • Letter |

    Jawless fish were recently shown to possess T- and B-like lymphocytes expressing diverse assembled antigen receptors. This study identifies and characterizes lympho-epithelial thymus-like structures at the tips of gill filaments of lamprey larvae, thus providing evidence that the similarities underlying the adaptive immune systems of both types of vertebrate appear to extend to primary lymphoid organs.

    • Baubak Bajoghli
    • , Peng Guo
    •  & Thomas Boehm

  • Books & Arts |

    Autism's broad diagnosis has fuelled fears about vaccines despite no evidence for a link, finds Melvin Konner.

    • Melvin Konner

  • News & Views |

    The transformation of tadpole to frog and of caterpillar to butterfly are two of the more obvious examples of metamorphosis. But molecular shape-shifting may occur in each of us as part of our innate antibacterial defence system. See Letter p.419

    • Robert I. Lehrer

  • Letter |

    This paper shows that the activity of human beta-defensin 1 is regulated by its redox status, with enhanced antibiotic killing activity under reducing conditions as they are found in the distal colon. This is believed to serve to protect the healthy intestinal epithelium against potentially harmful colonization by commensal bacteria and opportunistic fungi. In vitro evidence implicates thioredoxin as the likely reducing agent.

    • Bjoern O. Schroeder
    • , Zhihong Wu
    •  & Jan Wehkamp

  • Letter |

    This study finds frequent mutations in MYD88 in the activated B-cell-like subtype of diffuse large B-cell lymphoma and, with lower frequency, in mucosa-associated lymphoid tissue lymphomas. MYD88 mediates signalling by Toll-like receptors, and the mutations, most of which affect the same amino acid, are shown to activate the pathway and promote cancer cell survival.

    • Vu N. Ngo
    • , Ryan M. Young
    •  & Louis M. Staudt

  • Letter |

    Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.

    • Shan Zha
    • , Chunguang Guo
    •  & Frederick W. Alt

  • Letter |

    Antigen receptor loci contain numerous gene segments that are recombined in response to antigen stimulation. The RAG endonuclease makes the double-strand breaks that initiate recombination. The ends of these breaks are hairpins that can only be cleaved by the Artemis nuclease. Here, it is shown that the specificity for Artemis is dictated by the histone protein H2AX, in cooperation with the repair protein MDC-1. In the absence of H2AX, another nuclease, CtIP, can open the ends but they are not joined efficiently; this leads to genomic instability.

    • Beth A. Helmink
    • , Anthony T. Tubbs
    •  & Barry P. Sleckman

  • Letter |

    Post-translationally modified histones are recognized by effector proteins which contain specific binding modules; for example, the bromodomain-containing BET proteins bind acetylated lysine residues during gene activation. Here a synthetic small molecule is described that interferes with the binding of certain BET family members to acetylated histones. The compound inhibits activation of pro-inflammatory genes in macrophages and has activity in a mouse model of inflammatory disease.

    • Edwige Nicodeme
    • , Kate L. Jeffrey
    •  & Alexander Tarakhovsky

  • News |

    First affordable and effective weapon against killer meningococcal meningitis A rolled out in Africa.

    • Declan Butler

  • News & Views |

    Data from several recent studies on the dynamics of regulatory T cells — which suppress excessive immune responses — do not add up. Collective analysis of the observations may reconcile the differences between them.

    • Shimon Sakaguchi

  • Letter |

    Natural killer cells and cytotoxic T cells kill virus-infected and malignant cells, releasing the pore-forming protein perforin in the process. Perforin is required for the delivery of pro-apoptotic granzymes to the target cell. These authors present the crystal structure of a perforin monomer together with a cryo-electron microscopy reconstruction of the oligomeric pore. Perforin monomers within the pore are arranged with an inside-out orientation relative to the structurally homologous monomers of cholesterol-dependent cytolysins.

    • Ruby H. P. Law
    • , Natalya Lukoyanova
    •  & James C. Whisstock

  • Letter |

    CD4+ T cells that selectively produce interleukin (IL)-17 (TH17 cells) are essential for host defence and autoimmunity. It has been thought that IL-6 and transforming growth factor (TGF)-β1 are the factors responsible for initiating the specification of TH17 cells. Here, however, it is shown that TH17 differentiation can occur in the absence of TGF-β signalling. IL-6, IL-23 and IL-1β effectively induced IL-17 production in naive precursors. These data reveal an alternative mode for TH17 differentiation and the importance of IL-23.

    • Kamran Ghoreschi
    • , Arian Laurence
    •  & John J. O’Shea

  • News & Views |

    The T-cell receptor on the surface of T cells requires antigen recognition to function. Structural studies reveal that its predecessor, the pre-T-cell receptor, is much more independent. See Letter p.844

    • Bernard Malissen
    •  & Hervé Luche

  • Letter |

    The pre-T-cell antigen receptor mediates early T-cell development and differentiation. These authors report its structure and explain how the head-to-tail dimeric arrangement allows the interaction of the pre-Tα domain with any variable β domain, and provides the basis for ligand-independent signalling.

    • Siew Siew Pang
    • , Richard Berry
    •  & Jamie Rossjohn

  • Letter |

    Apoptotic cells discharge ATP and UTP, which act as 'find-me' signals for phagocytes that in turn engulf dying cells before potentially harmful cellular contents are released. These authors show that the release of ATP and UTP is exclusively by means of the plasma membrane channel pannexin 1, which is opened specifically by caspase activity.

    • Faraaz B. Chekeni
    • , Michael R. Elliott
    •  & Kodi S. Ravichandran

  • Letter |

    Here it is shown that the end products of lipid oxidation — ω-(2-carboxyethyl) pyrrole and other related pyrroles — are generated during inflammation and wound healing, and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in murine and human melanomas. These carboxyalkylpyrroles are recognized by Toll-like receptor 2 on endothelial cells, setting off a chain of events that leads to the growth of new blood vessels.

    • Xiaoxia Z. West
    • , Nikolay L. Malinin
    •  & Tatiana V. Byzova

  • Letter |

    During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. Here, the monoclonal antibodies produced in two infected subjects in response to human immunodeficiency virus (HIV) glycoprotein have been analysed. The results provide evidence for polyreactivity, which may be required when the density of glycoprotein spikes is so low that bivalent binding is unlikely.

    • Hugo Mouquet
    • , Johannes F. Scheid
    •  & Michel C. Nussenzweig

  • News & Views |

    Spikes on the surface of HIV to which antibodies can bind are sparse. One of nature's solutions is to sometimes produce antibodies that bind tightly to a spike with one arm and grab another structure with the other arm. See Letter p.591

    • Andreas Plückthun

  • Letter |

    Progestins, used in contraceptives and hormone replacement therapy, have been linked to breast cancer. These authors provide a mechanistic basis for this association. They show in a mouse model that synthetic progestins can promote mammary tumour formation by inducing RANKL (receptor activator of NF-KB ligand), which acts on mammary epithelial cells through the RANKL receptor RANK.

    • Daniel Schramek
    • , Andreas Leibbrandt
    •  & Josef M. Penninger

  • News |

    A way to nail down the shape of a viral protein segment could spur vaccine development.

    • Alla Katsnelson

  • Article |

    Salmonella enterica serotype Typhimurium causes acute gut inflammation, which promotes the growth of the pathogen through unknown mechanisms. It is now shown that the reactive oxygen species generated during inflammation react with host-derived sulphur compounds to produce tetrathionate, which the pathogen uses as a terminal electron acceptor to support its growth. The ability to use tetrathionate provides the pathogen with a competitive advantage over bacteria that lack this property.

    • Sebastian E. Winter
    • , Parameth Thiennimitr
    •  & Andreas J. Bäumler

  • Editorial |

    Plan to cull badgers in England shows the new government does not respect scientific advice.

  • News & Views |

    How does a Salmonella pathogen outcompete beneficial intestinal microorganisms? It triggers an immune response that generates a compound from intestinal gas that it can utilize as an energy source. See Article p. 426

    • Samuel I. Miller

  • Letter |

    Immune cells that recognize 'self' tissues need to be eliminated or controlled in order to prevent autoimmune diseases. Here, a T-cell population is delineated that is necessary to maintain self tolerance in mice. Genetic disruption of the inhibitory interaction between these CD8+ T cells and their target Qa-1+ follicular T-helper cells results in a lethal systemic-lupus-erythematosus-like autoimmune disease.

    • Hye-Jung Kim
    • , Bert Verbinnen
    •  & Harvey Cantor

  • News |

    Fired researcher's allegations of misconduct prompt university to investigate vaccine trial.

    • Emma Marris

  • Letter |

    Human immunodeficiency virus (HIV) fails to induce interferon in the cells that it infects, but the underlying mechanisms are not known. These authors show that the virus can in fact activate the interferon pathway in dendritic cells when the usual block to infection is bypassed. Dendritic cell activation depends on the HIV-1 capsid/cyclophilin A interaction, which is known to have a role in HIV-1 infectivity.

    • Nicolas Manel
    • , Brandon Hogstad
    •  & Dan R. Littman

  • Letter |

    B cells are activated by many different antigens to produce appropriate antibodies. B cells express up to 120,000 B-cell antigen receptor (BCR) complexes on their surface, but how do these complexes remain silent on resting B cells, and how are they activated? It is found here that the BCR on resting cells forms oligomers, and that these may be an autoinhibited form of the receptor. Disruption of the oligomer shifts B cells towards activation.

    • Jianying Yang
    •  & Michael Reth

  • Letter |

    The thymus contains thymic epithelial cells (TECs), which form a complex three-dimensional network organized into cortical and medullary compartments. It is shown here that these cells are plastic. Clonogenic TECs can acquire new properties when exposed to the skin microenvironment; under such conditions, they can permanently adopt the fate of hair follicle multipotent stem cells. Hence, microenvironmental cues can be sufficient to re-direct epithelial cell fate.

    • Paola Bonfanti
    • , Stéphanie Claudinot
    •  & Yann Barrandon

  • Letter |

    Here, the human immune response to infection with Mycobacterium tuberculosis has been characterized by transcriptional profiling. The results show that active tuberculosis correlates with a particular transcriptional signature that is dominated by a neutrophil-driven interferon-inducible gene profile. The study provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the tuberculosis epidemic.

    • Matthew P. R. Berry
    • , Christine M. Graham
    •  & Anne O’Garra

  • Letter |

    Here, a new type of behaviour of receptor–ligand bonds has been identified, by using a new method that links receptor and ligand in a single molecule to measure binding and unbinding. The binding of von Willebrand factor to the glycoprotein Ib α subunit on the surface of platelets is important for coagulation. This receptor–ligand bond is now shown to have two distinct states, one seen at low force and a second that has greater force resistance. This has implications for how increased blood flow activates platelet plug formation.

    • Jongseong Kim
    • , Cheng-Zhong Zhang
    •  & Timothy A. Springer

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