Volume 17 Issue 3, March 2016

Volume 17 Issue 3

Regulatory T cells help mediate immunotolerance to self tissues. Chi and colleagues (p 277) find a crucial requirement for autophagy in orchestrating the suppressive activity of these cells in mice. The original image of hematoxylin-and-eosin–stained tissue by Peter Vogel shows extensive inflammation, fibrosis and infiltration of cells of the immune system in the esophagus. Artwork by Lewis Long.

Correspondence

Meeting Report

News and Views

  • News & Views |

    SHARPIN acts independently of the ubiquitin-assembly complex LUBAC to attenuate proximal signaling downstream of TCRs by inhibiting the interaction of Zap70 with the TCRζ chain through Lys63 (K63)-linked polyubiquitination. SHARPIN deficiency enhanced TCR signaling and impaired the development and function of Treg cells.

    • Melissa Bowman
    • , Fan Pan
    •  & Edward W Harhaj
  • News & Views |

    The NLRP3 inflammasome has broad biomedical relevance, but its activation mechanisms are incompletely understood. NEK7, a kinase that regulates microtubules during mitosis, is identified as a critical and selective upstream regulator of NLRP3 inflammasome activation.

    • Filip Van Hauwermeiren
    •  & Mohamed Lamkanfi
  • News & Views |

    An important new function for the phosphatase PTEN in regulating interferon responses to viral infection has been delineated. This finding could help explain the remarkable cancer selectivity of many oncolytic viruses.

    • Brian R Champion
    • , Kerry Fisher
    •  & Len Seymour
  • News & Views |

    The production of interleukin 12 (IL-12) and IL-23 in dendritic cells is strictly regulated via epigenetic silencing. This transcriptional repression is overcome with the help of the deubiquitinase Trabid and has functional implications in a mouse model of multiple sclerosis.

    • Inna S Afonina
    •  & Rudi Beyaert

Research Highlights

Review

  • Review Article |

    Inflammation is one of the hallmarks of cancer. Ben-Neriah and colleagues review the inflammatory networks underlying colorectal cancer.

    • Audrey Lasry
    • , Adar Zinger
    •  & Yinon Ben-Neriah

Articles

  • Article |

    PTEN functions as a tumor suppressor. Guo and colleagues now find PTEN also serves a critical role in antiviral innate immunity by inducing the production of type I interferon.

    • Shun Li
    • , Mingzhu Zhu
    • , Ruangang Pan
    • , Ting Fang
    • , Yuan-Yuan Cao
    • , Shuliang Chen
    • , Xiaolu Zhao
    • , Cao-Qi Lei
    • , Lin Guo
    • , Yu Chen
    • , Chun-Mei Li
    • , Eija Jokitalo
    • , Yuxin Yin
    • , Hong-Bing Shu
    •  & Deyin Guo
  • Article |

    NEK7 is a serine-threonine kinase linked to mitosis. Beutler and colleagues show that NEK7 is required for assembly of the NLRP3 inflammasome and restricts NLRP3 activation to interphase of the cell cycle.

    • Hexin Shi
    • , Ying Wang
    • , Xiaohong Li
    • , Xiaoming Zhan
    • , Miao Tang
    • , Maggy Fina
    • , Lijing Su
    • , David Pratt
    • , Chun Hui Bu
    • , Sara Hildebrand
    • , Stephen Lyon
    • , Lindsay Scott
    • , Jiexia Quan
    • , Qihua Sun
    • , Jamie Russell
    • , Stephanie Arnett
    • , Peter Jurek
    • , Ding Chen
    • , Vladimir V Kravchenko
    • , John C Mathison
    • , Eva Marie Y Moresco
    • , Nancy L Monson
    • , Richard J Ulevitch
    •  & Bruce Beutler
  • Article |

    The precise lineage relationship between innate lymphoid cells and lymphoid tissue–inducer cells is poorly understood. Using single-cell transcriptional analysis and cultures of fetal liver precursor cells, Bendelac and colleagues define the divergence of these cells.

    • Isabel E Ishizuka
    • , Sylvestre Chea
    • , Herman Gudjonson
    • , Michael G Constantinides
    • , Aaron R Dinner
    • , Albert Bendelac
    •  & Rachel Golub
  • Article |

    Regulatory T (Treg) cells have a distinct cellular metabolism compared to effector T cells. Chi and colleagues show that autophagy is required to maintain the functional integrity and metabolic homeostasis of Treg cells in the face of inflammatory environmental cues.

    • Jun Wei
    • , Lingyun Long
    • , Kai Yang
    • , Cliff Guy
    • , Sharad Shrestha
    • , Zuojia Chen
    • , Chuan Wu
    • , Peter Vogel
    • , Geoffrey Neale
    • , Douglas R Green
    •  & Hongbo Chi
  • Article |

    SHARPIN is a component of the linear-ubiquitin-chain–assembly complex that positively regulates activation of the transcription factor NF-κB. Liu and colleagues show that SHARPIN regulates TCR signaling independently of NF-κB and that its deficiency impairs Treg cell generation.

    • Yoon Park
    • , Hyung-seung Jin
    • , Justine Lopez
    • , Jeeho Lee
    • , Lujian Liao
    • , Chris Elly
    •  & Yun-Cai Liu
  • Article |

    Inflammation can boost antigen-specific adaptive immune responses. Ziegler and colleagues show that type I interferon-mediated inflammation can also affect bystander naive CD4+ T cells by transiently increasing their expression of Foxp3, which might limit aggressive responses against self-antigens.

    • Lucas J Thompson
    • , Jen-Feng Lai
    • , Andrea C Valladao
    • , Tennille D Thelen
    • , Zoe L Urry
    •  & Steven F Ziegler
  • Article |

    T cell anergy is a well-established phenomenon, but its physiological role is unclear. Mueller and colleagues demonstrate that anergic self-reactive T cells are present at steady state and that these are predisposed to generate peripheral regulatory T cells.

    • Lokesh A Kalekar
    • , Shirdi E Schmiel
    • , Sarada L Nandiwada
    • , Wing Y Lam
    • , Laura O Barsness
    • , Na Zhang
    • , Gretta L Stritesky
    • , Deepali Malhotra
    • , Kristen E Pauken
    • , Jonathan L Linehan
    • , M Gerard O'Sullivan
    • , Brian T Fife
    • , Kristin A Hogquist
    • , Marc K Jenkins
    •  & Daniel L Mueller
  • Article |

    T cells proliferate in response to cues provided by antigen-presenting cells or high concentrations of cytokines. Krummel and colleagues reveal a distinct requirement for the cytoskeletal protein septin 7 for cytokine-driven bystander T cell proliferation.

    • Adriana M Mujal
    • , Julia K Gilden
    • , Audrey Gérard
    • , Makoto Kinoshita
    •  & Matthew F Krummel
  • Article |

    The transcription factor Blimp-1 is required for the differentiation of activated B cells into plasmablasts. Nutt and colleagues show that plasma cells need Blimp-1 to maintain antibody production by regulating the kinase mTOR and unfolded-protein-response pathways.

    • Julie Tellier
    • , Wei Shi
    • , Martina Minnich
    • , Yang Liao
    • , Simon Crawford
    • , Gordon K Smyth
    • , Axel Kallies
    • , Meinrad Busslinger
    •  & Stephen L Nutt
  • Article |

    Blimp-1 is known to act as a transcriptional repressor by suppressing genes associated with mature and activated germinal center B cells. Busslinger and colleagues show that Blimp-1 can also directly activate gene expression in plasma cells, including those encoding proteins that regulate the production of membrane-bound immunoglobulin versus secreted immunoglobulin.

    • Martina Minnich
    • , Hiromi Tagoh
    • , Peter Bönelt
    • , Elin Axelsson
    • , Maria Fischer
    • , Beatriz Cebolla
    • , Alexander Tarakhovsky
    • , Stephen L Nutt
    • , Markus Jaritz
    •  & Meinrad Busslinger