Volume 17 Issue 12, December 2016

Volume 17 Issue 12

Microglia are resident macrophages in the central nervous system. Greter and colleagues (p 1397) demonstrate that the transcriptional regulator Sall1 is expressed specifically by microglia and is critical for microglial identity and homeostatic functions. The original image by Anne Buttgereit shows a three-dimensional reconstruction of a wild-type microglial cell stained with Iba-1. Artwork by Lewis Long.

News and Views

  • News & Views |

    Free heme released by hemolysis directly inhibits bacterial phagocytosis by macrophages via alterations of actin cytoskeletal dynamics.

    • Sioh-Yang Tan
    •  & Wolfgang Weninger
  • News & Views |

    Notch signaling promotes the maintenance of lung-resident CD8+ memory T cells that are transcriptionally poised for rapid effector responses but have heightened expression of inhibitory receptors, suggestive of tight regulation.

    • Sathi Wijeyesinghe
    •  & David Masopust
  • News & Views |

    Deficiency in the RASGRP1 guanine-nucleotide-exchange factor leads to a novel primary immunodeficiency with impaired activation and proliferation of T cells and B cells and defective killing by cytotoxic T cells and natural killer cells.

    • Jeroen P Roose

Research Highlights

Articles

  • Article |

    Boztug and colleagues identify an immunodeficient patient with a deficiency in the guanine-nucleotide-exchange factor RASGRP1. They find that human RASGRP1 is important for the function of T cells, B cells and NK cells and that it has a role in the regulation of the cytoskeleton.

    • Elisabeth Salzer
    • , Deniz Cagdas
    • , Miroslav Hons
    • , Emily M Mace
    • , Wojciech Garncarz
    • , Özlem Yüce Petronczki
    • , René Platzer
    • , Laurène Pfajfer
    • , Ivan Bilic
    • , Sol A Ban
    • , Katharina L Willmann
    • , Malini Mukherjee
    • , Verena Supper
    • , Hsiang Ting Hsu
    • , Pinaki P Banerjee
    • , Papiya Sinha
    • , Fabienne McClanahan
    • , Gerhard J Zlabinger
    • , Winfried F Pickl
    • , John G Gribben
    • , Hannes Stockinger
    • , Keiryn L Bennett
    • , Johannes B Huppa
    • , Loïc Dupré
    • , Özden Sanal
    • , Ulrich Jäger
    • , Michael Sixt
    • , Ilhan Tezcan
    • , Jordan S Orange
    •  & Kaan Boztug
  • Article |

    Knapp and colleagues show that elevated heme levels following hemolysis impair the control of bacterial proliferation by inhibiting phagocytosis and migration of human and mouse phagocytes independently of heme-iron acquisition by bacteria as a source of nutrients.

    • Rui Martins
    • , Julia Maier
    • , Anna-Dorothea Gorki
    • , Kilian V M Huber
    • , Omar Sharif
    • , Philipp Starkl
    • , Simona Saluzzo
    • , Federica Quattrone
    • , Riem Gawish
    • , Karin Lakovits
    • , Michael C Aichinger
    • , Branka Radic-Sarikas
    • , Charles-Hugues Lardeau
    • , Anastasiya Hladik
    • , Ana Korosec
    • , Markus Brown
    • , Kari Vaahtomeri
    • , Michelle Duggan
    • , Dontscho Kerjaschki
    • , Harald Esterbauer
    • , Jacques Colinge
    • , Stephanie C Eisenbarth
    • , Thomas Decker
    • , Keiryn L Bennett
    • , Stefan Kubicek
    • , Michael Sixt
    • , Giulio Superti-Furga
    •  & Sylvia Knapp
  • Article |

    Alveolar macrophages help maintain lung-tissue homeostasis despite constant microbial exposure. Zhang and colleagues show that the E3 ligase TRIM29 suppresses excessive proinflammatory responses by targeting the adaptor NEMO in alveolar macrophages.

    • Junji Xing
    • , Leiyun Weng
    • , Bin Yuan
    • , Zhuo Wang
    • , Li Jia
    • , Rui Jin
    • , Hongbo Lu
    • , Xian Chang Li
    • , Yong-Jun Liu
    •  & Zhiqiang Zhang
  • Article |

    Type 2 responses can be elicited by ILC2s and TH2 cells. Locksley and colleagues show that the epithelium-derived cytokines IL-25, IL-33 and TSLP are required for full effector activation of poised ILC2 and primed TH2 cell populations.

    • Steven J Van Dyken
    • , Jesse C Nussbaum
    • , Jinwoo Lee
    • , Ari B Molofsky
    • , Hong-Erh Liang
    • , Joshua L Pollack
    • , Rachel E Gate
    • , Genevieve E Haliburton
    • , Chun J Ye
    • , Alexander Marson
    • , David J Erle
    •  & Richard M Locksley
  • Article |

    Fibroblastic reticular cells influence the function of lymphocytes in secondary lymphoid organs. Ludewig and colleagues demonstrate that they also specifically restrain the activation of group 1 innate lymphoid cells in the presence of microbial stimulation to prevent immunopathology.

    • Cristina Gil-Cruz
    • , Christian Perez-Shibayama
    • , Lucas Onder
    • , Qian Chai
    • , Jovana Cupovic
    • , Hung-Wei Cheng
    • , Mario Novkovic
    • , Philipp A Lang
    • , Markus B Geuking
    • , Kathy D McCoy
    • , Shinya Abe
    • , Guangwei Cui
    • , Koichi Ikuta
    • , Elke Scandella
    •  & Burkhard Ludewig
  • Article |

    Microglia are CNS-resident macrophages, but studying their functions in health and disease has been challenging due to a lack of specific markers. Greter and colleagues identify the transcription factor Sall1 as being uniquely associated with microglia in the CNS, where it is important for defining their fate and homeostatic function.

    • Anne Buttgereit
    • , Iva Lelios
    • , Xueyang Yu
    • , Melissa Vrohlings
    • , Natalie R Krakoski
    • , Emmanuel L Gautier
    • , Ryuichi Nishinakamura
    • , Burkhard Becher
    •  & Melanie Greter
  • Article |

    The cytokine IL-18 can drive autoantibody production. Karlsson and colleagues show that such responses are limited by a three-way cellular interaction whereby splenic neutrophils activate both B cells and invariant natural killer T cells but the activated B cells are killed by FasL+ invariant natural killer T cells.

    • Thomas Hägglöf
    • , Saikiran K Sedimbi
    • , Jennifer L Yates
    • , Roham Parsa
    • , Briana Hauff Salas
    • , Robert A Harris
    • , Elizabeth A Leadbetter
    •  & Mikael C I Karlsson
  • Article |

    The CD4-versus-CD8 lineage ‘choice’ is a critical stage of thymocyte development. Singer and colleagues reveal that CD8 positive selection occurs in a defined time window and involves a compensatory mechanism that dynamically adjusts to TCR and cytokine signals.

    • Motoko Y Kimura
    • , Julien Thomas
    • , Xuguang Tai
    • , Terry I Guinter
    • , Miho Shinzawa
    • , Ruth Etzensperger
    • , Zhenhu Li
    • , Paul Love
    • , Toshinori Nakayama
    •  & Alfred Singer
  • Article |

    The identity and lineage potential of the embryonic thymus-seeding progenitors that first seed the embryonic thymic rudiment is unclear. Jacobsen and colleagues find that these cells do not include multipotent stem cells or T cell–restricted progenitors but instead are lympho-myeloid progenitors.

    • Tiago C Luis
    • , Sidinh Luc
    • , Takuo Mizukami
    • , Hanane Boukarabila
    • , Supat Thongjuea
    • , Petter S Woll
    • , Emanuele Azzoni
    • , Alice Giustacchini
    • , Michael Lutteropp
    • , Tiphaine Bouriez-Jones
    • , Harsh Vaidya
    • , Adam J Mead
    • , Deborah Atkinson
    • , Charlotta Böiers
    • , Joana Carrelha
    • , Iain C Macaulay
    • , Roger Patient
    • , Frederic Geissmann
    • , Claus Nerlov
    • , Rickard Sandberg
    • , Marella F T R de Bruijn
    • , C Clare Blackburn
    • , Isabelle Godin
    •  & Sten Eirik W Jacobsen
  • Article |

    Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH cell)-mediated antibody production. Sharpe and colleagues show that TFR cells induce a distinct suppressive state in TFH cells and B cells that can be reversed by the cytokine IL-21.

    • Peter T Sage
    • , Noga Ron-Harel
    • , Vikram R Juneja
    • , Debattama R Sen
    • , Seth Maleri
    • , Waradon Sungnak
    • , Vijay K Kuchroo
    • , W Nicholas Haining
    • , Nicolas Chevrier
    • , Marcia Haigis
    •  & Arlene H Sharpe
  • Article |

    T follicular helper (TFH) cells are important for the formation of germinal centers and antibody responses. Kubo and colleagues show that TH1 cells can induce a protective antibody response in the complete absence of TFH cells and germinal centers.

    • Kosuke Miyauchi
    • , Akiko Sugimoto-Ishige
    • , Yasuyo Harada
    • , Yu Adachi
    • , Yoshiko Usami
    • , Tomohiro Kaji
    • , Kentaro Inoue
    • , Hideki Hasegawa
    • , Takashi Watanabe
    • , Atsushi Hijikata
    • , Satoshi Fukuyama
    • , Tadashi Maemura
    • , Mariko Okada-Hatakeyama
    • , Osamu Ohara
    • , Yoshihiro Kawaoka
    • , Yoshimasa Takahashi
    • , Toshitada Takemori
    •  & Masato Kubo
  • Article |

    T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.

    • Valerie A Gerriets
    • , Rigel J Kishton
    • , Marc O Johnson
    • , Sivan Cohen
    • , Peter J Siska
    • , Amanda G Nichols
    • , Marc O Warmoes
    • , Aguirre A de Cubas
    • , Nancie J MacIver
    • , Jason W Locasale
    • , Laurence A Turka
    • , Andrew D Wells
    •  & Jeffrey C Rathmell

Resource

  • Resource |

    A goal of vaccination is to elicit and maintain tissue-resident memory T cells. Amsen and colleagues show human lung-resident memory CD8+ T cells express distinct transcriptional programs, including a role for Notch in cellular metabolism and maintenance.

    • Pleun Hombrink
    • , Christina Helbig
    • , Ronald A Backer
    • , Berber Piet
    • , Anna E Oja
    • , Regina Stark
    • , Giso Brasser
    • , Aldo Jongejan
    • , René E Jonkers
    • , Benjamin Nota
    • , Onur Basak
    • , Hans C Clevers
    • , Perry D Moerland
    • , Derk Amsen
    •  & René A W van Lier

Corrigenda

Erratum