Volume 18 Issue 7, July 2017

Volume 18 Issue 7

An imbalance in the lineage of immunosuppressive regulatory T cells (Treg cells) and that of the inflammatory TH17 subset of helper T cells is pivotal in the development of autoimmune and inflammatory diseases. Chen and colleagues (p 800; News and Views by McGeachy p 709) show that the transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells. The original image by Jing Geng, Dawang Zhou and Lanfen Chen shows that TAZ (purple) polymerizes and forms nuclear foci with the Treg cell–defining factor Foxp3 (red) and the TH17 cell master regulator RORgt (green). Artwork by Lewis Long.

Obituary

News and Views

  • News & Views |

    A study of polymorphisms in the sensor IFIH1 exposes the evolutionary trade-off between a robust antiviral type I interferon response and the risk of interferon-mediated inflammation.

    • Erika Della Mina
    • , Mathieu P Rodero
    •  & Yanick J Crow
  • News & Views |

    The Hippo signaling pathway regulates cellular proliferation and survival during tissue growth and cancer. In CD4+ T cells, members of the Hippo family modulate autoimmune inflammation by altering interactions between the transcription factors Foxp3 and RORγt; this reveals an unexpected non-canonical role for Hippo in adaptive immunity.

    • Mandy J McGeachy
  • News & Views |

    Chemokines are important components of the hematopoietic niche. The atypical chemokine receptor 1 (ACKR1), expressed on erythrocyte precursors, regulates myeloid differentiation.

    • Massimo Locati
    • , Alberto Mantovani
    •  & Raffaella Bonecchi
  • News & Views |

    Thymocytes must undergo positive selection to survive and differentiate. This process is regulated by the TCR-sensitive protein CHMPS by preventing Bcl2 oxidation and degradation.

    • Gerald P Morris
    •  & Stephen M Hedrick

Research Highlights

Reviews

  • Review Article |

    Autoimmunity can arise when tolerance mechanisms break down. Theofilopoulos and colleagues review how loss of peripheral tolerance, often driven by innate nucleic-acid sensors, leads to the activation of autoreactive lymphocytes that underlie many autoimmune diseases.

    • Argyrios N Theofilopoulos
    • , Dwight H Kono
    •  & Roberto Baccala
  • Review Article |

    Davis and colleagues review systems-biology approaches in immunology as a powerful means of understanding the immune system as a whole.

    • Mark M Davis
    • , Cristina M Tato
    •  & David Furman

Articles

  • Article |

    Intracellular detection of viral invasion triggers activation of the transcription factor IRF3 and antiviral interferon production. Fangfang Zhou and colleagues report that the transcription regulator YAP in the host restrains this process by preventing inadvertent spontaneous dimerization of IRF3 and its translocation to the nucleus.

    • Shuai Wang
    • , Feng Xie
    • , Feng Chu
    • , Zhengkui Zhang
    • , Bing Yang
    • , Tong Dai
    • , Liang Gao
    • , Lin Wang
    • , Li Ling
    • , Junling Jia
    • , Hans van Dam
    • , Jin Jin
    • , Long Zhang
    •  & Fangfang Zhou
  • Article |

    Single-nucleotide polymorphisms in the gene encoding the cytosolic viral sensor IFIH1 are linked to a variety of autoimmune diseases. Rawlings and colleagues demonstrate that one such common polymorphism results in IFIH1 with more-potent activation and can act synergistically with other genetic backgrounds to manifest autoimmune disease.

    • Jacquelyn A Gorman
    • , Christian Hundhausen
    • , John S Errett
    • , Amy E Stone
    • , Eric J Allenspach
    • , Yan Ge
    • , Tanvi Arkatkar
    • , Courtnee Clough
    • , Xuezhi Dai
    • , Socheath Khim
    • , Kathleen Pestal
    • , Denny Liggitt
    • , Karen Cerosaletti
    • , Daniel B Stetson
    • , Richard G James
    • , Mohamed Oukka
    • , Patrick Concannon
    • , Michael Gale Jr
    • , Jane H Buckner
    •  & David J Rawlings
  • Article |

    Genetic polymorphisms affect expression of the atypical chemokine receptor ACKR1 (Duffy) on nucleated erythrocyte precursors. Rot and colleagues show that loss of its expression alters hematopoiesis, yielding a distinct neutrophil population that rapidly exits the bloodstream to give an apparent ‘neutropenia’ phenotype.

    • Johan Duchene
    • , Igor Novitzky-Basso
    • , Aude Thiriot
    • , Maria Casanova-Acebes
    • , Mariaelvy Bianchini
    • , S Leah Etheridge
    • , Elin Hub
    • , Katrin Nitz
    • , Katharina Artinger
    • , Kathrin Eller
    • , Jorge Caamaño
    • , Thomas Rülicke
    • , Paul Moss
    • , Remco T A Megens
    • , Ulrich H von Andrian
    • , Andres Hidalgo
    • , Christian Weber
    •  & Antal Rot
  • Article |

    TCRβ+CD8αα+ intraepithelial lymphocytes arise from CD4CD8CD5+ thymic cells, but the exact precursor source has been not been established. Hogquist and colleagues identify two distinct thymic populations that both give rise mainly to gut-homing intraepithelial lymphocytes.

    • Roland Ruscher
    • , Rebecca L Kummer
    • , You Jeong Lee
    • , Stephen C Jameson
    •  & Kristin A Hogquist
  • Article |

    Thymocytes must undergo positive selection to survive and emigrate to the periphery as mature T cells. Glimcher and colleagues identify CHMP5 as a TCR-sensitive regulator of positive selection that acts by preventing oxidation and degradation of the pro-survival protein Bcl-2.

    • Stanley Adoro
    • , Kwang Hwan Park
    • , Sarah E Bettigole
    • , Raphael Lis
    • , Hee Rae Shin
    • , Heewon Seo
    • , Ju Han Kim
    • , Klaus-Peter Knobeloch
    • , Jae-Hyuck Shim
    •  & Laurie H Glimcher
  • Article |

    Wucherpfennig and colleagues show that the microRNA miR-31 increases the sensitivity of T cells to type I interferons, which interferes with effector T cell function during chronic infection.

    • Howell F Moffett
    • , Adam N R Cartwright
    • , Hye-Jung Kim
    • , Jernej Godec
    • , Jason Pyrdol
    • , Tarmo Äijö
    • , Gustavo J Martinez
    • , Anjana Rao
    • , Jun Lu
    • , Todd R Golub
    • , Harvey Cantor
    • , Arlene H Sharpe
    • , Carl D Novina
    •  & Kai W Wucherpfennig
  • Article |

    Hippo signaling controls cell and tissue growth. Geng et al. show that Hippo signaling is required for TH17 cell differentiation but inhibits Treg cell differentiation.

    • Jing Geng
    • , Shujuan Yu
    • , Hao Zhao
    • , Xiufeng Sun
    • , Xun Li
    • , Ping Wang
    • , Xiaolin Xiong
    • , Lixin Hong
    • , Changchuan Xie
    • , Jiahui Gao
    • , Yiran Shi
    • , Jiaqi Peng
    • , Randy L Johnson
    • , Nengming Xiao
    • , Linrong Lu
    • , Jiahuai Han
    • , Dawang Zhou
    •  & Lanfen Chen
  • Article |

    BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.

    • Behdad Afzali
    • , Juha Grönholm
    • , Jana Vandrovcova
    • , Charlotte O'Brien
    • , Hong-Wei Sun
    • , Ine Vanderleyden
    • , Fred P Davis
    • , Ahmad Khoder
    • , Yu Zhang
    • , Ahmed N Hegazy
    • , Alejandro V Villarino
    • , Ira W Palmer
    • , Joshua Kaufman
    • , Norman R Watts
    • , Majid Kazemian
    • , Olena Kamenyeva
    • , Julia Keith
    • , Anwar Sayed
    • , Dalia Kasperaviciute
    • , Michael Mueller
    • , Jason D Hughes
    • , Ivan J Fuss
    • , Mohammed F Sadiyah
    • , Kim Montgomery-Recht
    • , Joshua McElwee
    • , Nicholas P Restifo
    • , Warren Strober
    • , Michelle A Linterman
    • , Paul T Wingfield
    • , Holm H Uhlig
    • , Rahul Roychoudhuri
    • , Timothy J Aitman
    • , Peter Kelleher
    • , Michael J Lenardo
    • , John J O'Shea
    • , Nichola Cooper
    •  & Arian D J Laurence