Volume 20 Issue 3, March 2019

Volume 20 Issue 3

Fetal intestinal memory CD4 + T cells

Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.

See Koning et al.

IMAGE: Na Li COVER DESIGN: Erin Dewalt

Research Highlights

News & Views

  • News & Views |

    A multivalent vaccine that presents diverse influenza virus subtype H1 hemagglutinins on its surface induces broadly neutralizing antibodies in an animal model by displaying conserved epitopes at higher density than strain-specific epitopes.

    • Florian Krammer
  • News & Views |

    The zinc transporter ZIP7 positively regulates signaling via the BCR during early B cell development in mice and humans. Impairment of ZIP7 function results in a novel primary immunodeficiency.

    • Toshiyuki Fukada
    • , Shintaro Hojyo
    • , Takafumi Hara
    •  & Teruhisa Takagishi
  • News & Views |

    Combined immunotherapy using checkpoint blockade (anti-CTLA4 and anti-PD-1) and the DPP4 inhibitor sitagliptin reveals the existence of a T cell– and eosinophil-targeted immunotherapy approach for solid tumors.

    • Ariel Munitz
    •  & Simon Patrick Hogan
  • News & Views |

    In patients with rheumatoid arthritis, decreased abundance of the N-myristoyltransferase NMT1 in CD4+ T cells prevents N-myristoylation of the AMP-activated protein kinase AMPK and its localization to the lysosomal membrane, which leads to increased activation of the metabolic checkpoint kinase complex mTORC1 and proinflammatory T cell phenotypes.

    • David K. Finlay
  • News & Views |

    The transition of the fetus from the womb to the external world represents an extraordinary challenge. The generation of memory T cells before birth may serve an important role in preparation for this fundamental transition.

    • Ai Ing Lim
    • , Oliver J. Harrison
    •  & Yasmine Belkaid

Articles

  • Article |

    Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.

    • Clémence Hollande
    • , Jeremy Boussier
    • , James Ziai
    • , Tamaki Nozawa
    • , Vincent Bondet
    • , Wilson Phung
    • , Binfeng Lu
    • , Darragh Duffy
    • , Valerie Paradis
    • , Vincent Mallet
    • , Gérard Eberl
    • , Wendy Sandoval
    • , Jill M. Schartner
    • , Stanislas Pol
    • , Rosa Barreira da Silva
    •  & Matthew L. Albert
  • Article |

    Macrophages have important antitumor functions but can be evaded by tumor-expressed CD47-dependent ‘don’t-eat-me’ signals. Beatty and colleagues demonstrate that the Toll-like receptor 9 ligand CpG metabolically reprograms macrophages to overcome don’t-eat-me signals.

    • Mingen Liu
    • , Roddy S. O’Connor
    • , Sophie Trefely
    • , Kathleen Graham
    • , Nathaniel W. Snyder
    •  & Gregory L. Beatty
  • Article |

    Serpins are a large family of serine protease inhibitors. Jae Jung and colleagues show that SERPINB1 serves an endogenous regulatory role for pro-inflammatory caspases by preventing CARD–CARD polymerization and, hence, inflammasome activation.

    • Youn Jung Choi
    • , Stephanie Kim
    • , Younho Choi
    • , Travis B. Nielsen
    • , Jun Yan
    • , Alvin Lu
    • , Jianbin Ruan
    • , Hye-Ra Lee
    • , Hao Wu
    • , Brad Spellberg
    •  & Jae U. Jung
  • Article |

    Tissue-resident memory T cells (TRM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal TRM cells can also have key pathogenic roles in inflammatory bowel disease.

    • Sebastian Zundler
    • , Emily Becker
    • , Marta Spocinska
    • , Monique Slawik
    • , Loreto Parga-Vidal
    • , Regina Stark
    • , Maximilian Wiendl
    • , Raja Atreya
    • , Timo Rath
    • , Moritz Leppkes
    • , Kai Hildner
    • , Rocío López-Posadas
    • , Sören Lukassen
    • , Arif B. Ekici
    • , Clemens Neufert
    • , Imke Atreya
    • , Klaas P. J. M. van Gisbergen
    •  & Markus F. Neurath
  • Article |

    Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.

    • Na Li
    • , Vincent van Unen
    • , Tamim Abdelaal
    • , Nannan Guo
    • , Sofya A. Kasatskaya
    • , Kristin Ladell
    • , James E. McLaren
    • , Evgeny S. Egorov
    • , Mark Izraelson
    • , Susana M. Chuva de Sousa Lopes
    • , Thomas Höllt
    • , Olga V Britanova
    • , Jeroen Eggermont
    • , Noel F. C. C. de Miranda
    • , Dmitriy M. Chudakov
    • , David A. Price
    • , Boudewijn P. F. Lelieveldt
    •  & Frits Koning
  • Article |

    Pathogenic human CD4+ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.

    • Zhenke Wen
    • , Ke Jin
    • , Yi Shen
    • , Zhen Yang
    • , Yinyin Li
    • , Bowen Wu
    • , Lu Tian
    • , Stanford Shoor
    • , Niall E. Roche
    • , Jorg J. Goronzy
    •  & Cornelia M. Weyand
  • Article |

    Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

    • Brian C. Miller
    • , Debattama R. Sen
    • , Rose Al Abosy
    • , Kevin Bi
    • , Yamini V. Virkud
    • , Martin W. LaFleur
    • , Kathleen B. Yates
    • , Ana Lako
    • , Kristen Felt
    • , Girish S. Naik
    • , Michael Manos
    • , Evisa Gjini
    • , Juhi R. Kuchroo
    • , Jeffrey J. Ishizuka
    • , Jenna L. Collier
    • , Gabriel K. Griffin
    • , Seth Maleri
    • , Dawn E. Comstock
    • , Sarah A. Weiss
    • , Flavian D. Brown
    • , Arpit Panda
    • , Margaret D. Zimmer
    • , Robert T. Manguso
    • , F. Stephen Hodi
    • , Scott J. Rodig
    • , Arlene H. Sharpe
    •  & W. Nicholas Haining
  • Article |

    Stemness is crucial for the maintenance of long-term T cell memory. Gattinoni and colleagues demonstrate that the transcription factor c-Myb is essential for the establishment of a stemness program in the CD8+ T cell memory compartment.

    • Sanjivan Gautam
    • , Jessica Fioravanti
    • , Wei Zhu
    • , John B. Le Gall
    • , Philip Brohawn
    • , Neal E. Lacey
    • , Jinhui Hu
    • , James D. Hocker
    • , Nga Voong Hawk
    • , Veena Kapoor
    • , William G. Telford
    • , Devikala Gurusamy
    • , Zhiya Yu
    • , Avinash Bhandoola
    • , Hai-Hui Xue
    • , Rahul Roychoudhuri
    • , Brandon W. Higgs
    • , Nicholas P. Restifo
    • , Timothy P. Bender
    • , Yun Ji
    •  & Luca Gattinoni
  • Article |

    Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.

    • Consuelo Anzilotti
    • , David J. Swan
    • , Bertrand Boisson
    • , Mukta Deobagkar-Lele
    • , Catarina Oliveira
    • , Pauline Chabosseau
    • , Karin R. Engelhardt
    • , Xijin Xu
    • , Rui Chen
    • , Luis Alvarez
    • , Rolando Berlinguer-Palmini
    • , Katherine R. Bull
    • , Eleanor Cawthorne
    • , Adam P. Cribbs
    • , Tanya L. Crockford
    • , Tarana Singh Dang
    • , Amy Fearn
    • , Emma J. Fenech
    • , Sarah J. de Jong
    • , B. Christoffer Lagerholm
    • , Cindy S. Ma
    • , David Sims
    • , Bert van den Berg
    • , Yaobo Xu
    • , Andrew J. Cant
    • , Gary Kleiner
    • , T. Ronan Leahy
    • , M. Teresa de la Morena
    • , Jennifer M. Puck
    • , Ralph S. Shapiro
    • , Mirjam van der Burg
    • , J. Ross Chapman
    • , John C. Christianson
    • , Benjamin Davies
    • , John A. McGrath
    • , Stefan Przyborski
    • , Mauro Santibanez Koref
    • , Stuart G. Tangye
    • , Andreas Werner
    • , Guy A. Rutter
    • , Sergi Padilla-Parra
    • , Jean-Laurent Casanova
    • , Richard J. Cornall
    • , Mary Ellen Conley
    •  & Sophie Hambleton
  • Article |

    Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

    • Masaru Kanekiyo
    • , M. Gordon Joyce
    • , Rebecca A. Gillespie
    • , John R. Gallagher
    • , Sarah F. Andrews
    • , Hadi M. Yassine
    • , Adam K. Wheatley
    • , Brian E. Fisher
    • , David R. Ambrozak
    • , Adrian Creanga
    • , Kwanyee Leung
    • , Eun Sung Yang
    • , Seyhan Boyoglu-Barnum
    • , Ivelin S. Georgiev
    • , Yaroslav Tsybovsky
    • , Madhu S. Prabhakaran
    • , Hanne Andersen
    • , Wing-Pui Kong
    • , Ulrich Baxa
    • , Kathryn L. Zephir
    • , Julie E. Ledgerwood
    • , Richard A. Koup
    • , Peter D. Kwong
    • , Audray K. Harris
    • , Adrian B. McDermott
    • , John R. Mascola
    •  & Barney S. Graham

Amendments & Corrections