Volume 17 Issue 5, May 2016

Volume 17 Issue 5

The physiological function of the mammalian chitinase AMCase is unclear. Wynn and colleagues (p 538) show that it is dispensable for allergic lung inflammation but is necessary for the clearance of intestinal helminths. The original image by Ian Moore and Kevin Bock shows a cross-section of a bronchiole from the lungs of a mouse exposed to helminth eggs. Artwork by Lewis Long.

Correspondence

News and Views

  • News & Views |

    Patients with XLPDR are found to carry an intronic hypomorphic mutation in the gene encoding the catalytic subunit of DNA polymerase-α. Patients' cells display low levels of cytoplasmic RNA:DNA hybrids, which increases the expression of interferon-α-induced genes, a hallmark of monogenic 'type I interferonopathies'.

    • Isabelle Meyts
    •  & Jean-Laurent Casanova
  • News & Views |

    Studies using genetic tools have identified the distinct dendritic cell subsets that ensure tolerance to oral antigens in the antigen-rich environment of the gut and suggest a 'division of labor' for protective immunity.

    • Reinhard Hinterleitner
    •  & Bana Jabri
  • News & Views |

    Chronic viral infections are characterized by ongoing inflammation and a dysfunctional T cell response, which results in a failure of the host to clear the pathogen. Now these two hallmarks of infection have been linked by the classic pro-inflammatory cytokine tumor-necrosis factor.

    • Amy E Baxter
    •  & Daniel E Kaufmann
  • News & Views |

    Regulatory T cells must limit activation of the metabolic checkpoint kinase mTOR to maintain their identity. The lipid ceramide serves a unique role in this process by inducing phosphatase PP2A–mediated inhibition of the mTORC1 complex.

    • Greg M Delgoffe

Research Highlights

Perspectives

  • Perspective |

    Bedoui and colleagues discuss the naive state of conventional T cells as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effectors, and also offers a relevant discrimination criterion between innate and adaptive lymphocytes.

    • Sammy Bedoui
    • , Thomas Gebhardt
    • , Georg Gasteiger
    •  & Wolfgang Kastenmüller

Articles

  • Article |

    The causative mechanism for the immunodeficiency and autoinflammatory disease XLPDR is unknown. Burstein and colleagues show that XLPDR is caused by disruption of POLA1, which encodes a DNA polymerase subunit; this, in turn, leads to dysregulated production of type I interferons.

    • Petro Starokadomskyy
    • , Terry Gemelli
    • , Jonathan J Rios
    • , Chao Xing
    • , Richard C Wang
    • , Haiying Li
    • , Vladislav Pokatayev
    • , Igor Dozmorov
    • , Shaheen Khan
    • , Naoteru Miyata
    • , Guadalupe Fraile
    • , Prithvi Raj
    • , Zhe Xu
    • , Zigang Xu
    • , Lin Ma
    • , Zhimiao Lin
    • , Huijun Wang
    • , Yong Yang
    • , Dan Ben-Amitai
    • , Naama Orenstein
    • , Huda Mussaffi
    • , Eulalia Baselga
    • , Gianluca Tadini
    • , Eyal Grunebaum
    • , Adrijan Sarajlija
    • , Konrad Krzewski
    • , Edward K Wakeland
    • , Nan Yan
    • , Maria Teresa de la Morena
    • , Andrew R Zinn
    •  & Ezra Burstein
  • Article |

    Irradiation to condition hosts for bone marrow transplantation leads to alterations in intestinal microbiota. Reddy and colleagues demonstrate that these changes result in reduced butyrate production and breakdown of intestinal barrier function.

    • Nathan D Mathewson
    • , Robert Jenq
    • , Anna V Mathew
    • , Mark Koenigsknecht
    • , Alan Hanash
    • , Tomomi Toubai
    • , Katherine Oravecz-Wilson
    • , Shin-Rong Wu
    • , Yaping Sun
    • , Corinne Rossi
    • , Hideaki Fujiwara
    • , Jaeman Byun
    • , Yusuke Shono
    • , Caroline Lindemans
    • , Marco Calafiore
    • , Thomas M Schmidt
    • , Kenya Honda
    • , Vincent B Young
    • , Subramaniam Pennathur
    • , Marcel van den Brink
    •  & Pavan Reddy
  • Article |

    Activation of the transcription factor IRF3 is a key event in antiviral responses. Lichty and colleagues show that recruitment of the mTOR downstream effector S6K1 to the STING-TBK1 signaling complex is required for the activation of IRF3 after infection with DNA viruses.

    • Fuan Wang
    • , Tommy Alain
    • , Kristy J Szretter
    • , Kyle Stephenson
    • , Jonathan G Pol
    • , Matthew J Atherton
    • , Huy-Dung Hoang
    • , Bruno D Fonseca
    • , Chadi Zakaria
    • , Lan Chen
    • , Zainab Rangwala
    • , Adam Hesch
    • , Eva Sin Yan Chan
    • , Carly Tuinman
    • , Mehul S Suthar
    • , Zhaozhao Jiang
    • , Ali A Ashkar
    • , George Thomas
    • , Sara C Kozma
    • , Michael Gale Jr
    • , Katherine A Fitzgerald
    • , Michael S Diamond
    • , Karen Mossman
    • , Nahum Sonenberg
    • , Yonghong Wan
    •  & Brian D Lichty
  • Article |

    14-3-3ɛ serves a crucial function in antiviral immunity by mediating the translocation of RIG-I from the cytosol to mitochondria. Chan and Gack have found that the NS3 protein of Dengue virus binds to 14-3-3ɛ via a highly conserved phosphomimetic motif and thereby blocks RIG-I translocation and antiviral signaling.

    • Ying Kai Chan
    •  & Michaela U Gack
  • Article |

    MR1 molecules present bacterial metabolites to MAIT innate lymphocytes, but the processing and presentation pathway of these ligands are unclear. McCluskey, Rossjohn, Villadangos and colleagues demonstrate that MR1 ligands bind in the ER, which initiates trafficking to the plasma membrane and subsequent presentation.

    • Hamish E G McWilliam
    • , Sidonia B G Eckle
    • , Alex Theodossis
    • , Ligong Liu
    • , Zhenjun Chen
    • , Jacinta M Wubben
    • , David P Fairlie
    • , Richard A Strugnell
    • , Justine D Mintern
    • , James McCluskey
    • , Jamie Rossjohn
    •  & Jose A Villadangos
  • Article |

    The physiological function of the mammalian chitinase AMCase is unclear. Wynn and colleagues show that it is dispensable for allergic lung inflammation but is necessary for clearance of intestinal helminths.

    • Kevin M Vannella
    • , Thirumalai R Ramalingam
    • , Kevin M Hart
    • , Rafael de Queiroz Prado
    • , Joshua Sciurba
    • , Luke Barron
    • , Lee A Borthwick
    • , Allen D Smith
    • , Margaret Mentink-Kane
    • , Sandra White
    • , Robert W Thompson
    • , Allen W Cheever
    • , Kevin Bock
    • , Ian Moore
    • , Lori J Fitz
    • , Joseph F Urban Jr
    •  & Thomas A Wynn
  • Article |

    The subsets of antigen presenting cells (APCs) that mediate tolerance to oral antigens remain unclear. Mucida and colleagues use lineage-specific depletion of APCs to show that monocyte-derived APCs are dispensable, while classical dendritic cells are critical, for the induction of regulatory T cells and oral tolerance.

    • Daria Esterházy
    • , Jakob Loschko
    • , Mariya London
    • , Veronica Jove
    • , Thiago Y Oliveira
    •  & Daniel Mucida
  • Article |

    Regulatory T cells use a distinct metabolism to exert their regulatory function. Tsokos and colleagues show that the phosphatase PP2A suppresses the metabolic-checkpoint kinase complex mTORC1 in these cells and is necessary for their function. PP2A activity is regulated by the cellular abundance of ceramide via a transcription factor Foxp3–dependent feedback mechanism.

    • Sokratis A Apostolidis
    • , Noé Rodríguez-Rodríguez
    • , Abel Suárez-Fueyo
    • , Nikolina Dioufa
    • , Esra Ozcan
    • , José C Crispín
    • , Maria G Tsokos
    •  & George C Tsokos
  • Article |

    The receptor tyrosine phosphatase CD45 has an important role in T cell activation. Davis and colleagues resolve the structure of CD45 and provide molecular insights into how it contributes to productive T cell receptor triggering.

    • Veronica T Chang
    • , Ricardo A Fernandes
    • , Kristina A Ganzinger
    • , Steven F Lee
    • , Christian Siebold
    • , James McColl
    • , Peter Jönsson
    • , Matthieu Palayret
    • , Karl Harlos
    • , Charlotte H Coles
    • , E Yvonne Jones
    • , Yuan Lui
    • , Elizabeth Huang
    • , Robert J C Gilbert
    • , David Klenerman
    • , A Radu Aricescu
    •  & Simon J Davis
  • Article |

    Inflammasome activation triggers the release of active interleukin 1β (IL-1β). Li and colleagues show that TH17 cells can release IL-1β upon T cell antigen receptor and ATP stimulation via an ASC–NLPR3–caspase-8 axis, thereby contributing to neuroinflammation.

    • Bradley N Martin
    • , Chenhui Wang
    • , Cun-jin Zhang
    • , Zizhen Kang
    • , Muhammet Fatih Gulen
    • , Jarod A Zepp
    • , Junjie Zhao
    • , Guanglin Bian
    • , Jeong-su Do
    • , Booki Min
    • , Paul G Pavicic Jr
    • , Caroline El-Sanadi
    • , Paul L Fox
    • , Aoi Akitsu
    • , Yoichiro Iwakura
    • , Anasuya Sarkar
    • , Mark D Wewers
    • , William J Kaiser
    • , Edward S Mocarski
    • , Marc E Rothenberg
    • , Amy G Hise
    • , George R Dubyak
    • , Richard M Ransohoff
    •  & Xiaoxia Li
  • Article |

    Functional T cell exhaustion occurs during chronic viral infection or in tumor settings. Beyer et al. report that chronic inflammation mediated by the cytokine TNF is responsible for this dysfunction and that blockade of this pathway restores immune system–mediated control of viral infection.

    • Marc Beyer
    • , Zeinab Abdullah
    • , Jens M Chemnitz
    • , Daniela Maisel
    • , Jil Sander
    • , Clara Lehmann
    • , Yasser Thabet
    • , Prashant V Shinde
    • , Lisa Schmidleithner
    • , Maren Köhne
    • , Jonel Trebicka
    • , Robert Schierwagen
    • , Andrea Hofmann
    • , Alexey Popov
    • , Karl S Lang
    • , Annette Oxenius
    • , Thorsten Buch
    • , Christian Kurts
    • , Mathias Heikenwalder
    • , Gerd Fätkenheuer
    • , Philipp A Lang
    • , Pia Hartmann
    • , Percy A Knolle
    •  & Joachim L Schultze