Volume 12 Issue 5, May 2011

Volume 12 Issue 5

Secretion of the chemokine CXCL12 and its deposition on the apical surface of primary human bone marrow stromal cells is dependent on cell-cell contact, as described by Schajnovitz and colleagues (p 391; see also News and Views by Milsom and Trumpp, p 377). Original fluorescence microscopy image shows the presentation of functional CXCL12 (green) by contacting primary human bone marrow stromal cells in vitro. Original image by Amir Schajnovitz. Artwork by Lewis Long.

Editorial

  • Editorial |

    Budget battles in the US Congress are precipitating higher costs at government facilities, including federal funding of biomedical research.

Obituary

Commentary

  • Commentary |

    Despite enormous progress in basic research, there are many gaps in understanding human immunity. Here we describe how new investigational tools and computational methods promise to improve the diagnosis, prognosis and therapy of the many diseases with components from the immune system.

    • Ronald N Germain
    •  & Pamela L Schwartzberg

News and Views

  • News & Views |

    B cell generation is disturbed in four newly identified mouse mutants bearing X-linked mutations in the gene encoding the ATPase ATP11C. These findings suggest that the distribution of membrane phospholipids confers a yet-to-be delineated developmental signal.

    • Marcus R Clark
  • News & Views |

    In addition to their classical function in antigen presentation and their lesser known ability to act as signal transducers, major histocompatibility complex class II molecules are now shown to promote Toll-like receptor signaling. This intriguing role requires intracellular association with the kinase Btk and the costimulatory molecule CD40.

    • Ghada S Hassan
    •  & Walid Mourad
  • News & Views |

    The interaction between hematopoietic stem cells and their niche is critical for the lifelong maintenance of the blood system. New research shows that crosstalk between stromal components of the niche mediates secretion of the chemokine CXCL12.

    • Michael D Milsom
    •  & Andreas Trumpp
  • News & Views |

    The inflammasome has been linked to metabolic disorders such as obesity and type 2 diabetes. Data now suggest that the crosstalk between the inflammasome and autophagy critically mediates cytoplasmic receptor NLRP3–dependent activation of the inflammasome by the saturated fatty acids contained in a high-fat diet.

    • Augustine M K Choi
    •  & Kiichi Nakahira

Research Highlights

Review

Articles

  • Article |

    The chemokine CXCL12 is essential for hematopoietic stem cell function. Lapidot and colleagues report that secretion of CXCL12 from bone marrow stromal cells is a cell contact–dependent event, mediated by connexin-43 and connexin-45 gap junctions.

    • Amir Schajnovitz
    • , Tomer Itkin
    • , Gabriele D'Uva
    • , Alexander Kalinkovich
    • , Karin Golan
    • , Aya Ludin
    • , Dror Cohen
    • , Ziv Shulman
    • , Abraham Avigdor
    • , Arnon Nagler
    • , Orit Kollet
    • , Rony Seger
    •  & Tsvee Lapidot
  • Article |

    Obesity is characterized by chronic inflammation, but the triggers for this remain unclear. Ting and colleagues demonstrate that a high fat diet activates the inflammasome, resulting in IL-1β release and insulin resistance.

    • Haitao Wen
    • , Denis Gris
    • , Yu Lei
    • , Sushmita Jha
    • , Lu Zhang
    • , Max Tze-Han Huang
    • , Willie June Brickey
    •  & Jenny P-Y Ting
  • Article |

    Developing B cells show enhanced sensitivity to negatively selecting signals. Weiss and colleagues show that calcium signals arising from activation of the calcium sensor STIM1 lead to activation of Erk and apoptosis via a protein kinase C-δ and the guanine nucleotide-exchange factor RasGRP1-dependent pathway in transitional self-reactive B cells.

    • Andre Limnander
    • , Philippe Depeille
    • , Tanya S Freedman
    • , Jen Liou
    • , Michael Leitges
    • , Tomohiro Kurosaki
    • , Jeroen P Roose
    •  & Arthur Weiss
  • Article |

    B cells arise via a precise developmental pathway. Goodnow and Beutler report that mice bearing mutations in Atp11c, which encodes a phosphatidylserine 'flippase', have defective B cell generation in the adult bone marrow.

    • Owen M Siggs
    • , Carrie N Arnold
    • , Christoph Huber
    • , Elaine Pirie
    • , Yu Xia
    • , Pei Lin
    • , David Nemazee
    •  & Bruce Beutler
  • Article |

    B cells arise via a precise developmental pathway. Goodnow and Beutler report that mice bearing mutations in Atp11c, which encodes a phosphatidylserine 'flippase', have defective B cell generation in the adult bone marrow.

    • Mehmet Yabas
    • , Charis E Teh
    • , Sandra Frankenreiter
    • , Dennis Lal
    • , Carla M Roots
    • , Belinda Whittle
    • , Daniel T Andrews
    • , Yafei Zhang
    • , Narci C Teoh
    • , Jonathan Sprent
    • , Lina E Tze
    • , Edyta M Kucharska
    • , Jennifer Kofler
    • , Geoffrey C Farell
    • , Stefan Bröer
    • , Christopher C Goodnow
    •  & Anselm Enders
  • Article |

    Chronic stimulation of lymphocytes results in upregulation of immunomodulatory IL-10, but the molecular mechanisms of this process have remained unknown. Kubo and colleagues demonstrate that the transcription factor E4BP4 is responsible for this plasticity.

    • Yasutaka Motomura
    • , Hiroshi Kitamura
    • , Atsushi Hijikata
    • , Yuko Matsunaga
    • , Koichiro Matsumoto
    • , Hiromasa Inoue
    • , Koji Atarashi
    • , Shohei Hori
    • , Hiroshi Watarai
    • , Jinfang Zhu
    • , Masaru Taniguchi
    •  & Masato Kubo