Volume 21 Issue 6, June 2015

Article

  • Article |

    Deletion of the transcription factor Irf5 in macrophages leads to expansion of the subcutaneous fat depot but restriction of the visceral fat during obesity, resulting in improved insulin sensitivity

    • Elise Dalmas
    • , Amine Toubal
    • , Fawaz Alzaid
    • , Katrina Blazek
    • , Hayley L Eames
    • , Kristell Lebozec
    • , Maria Pini
    • , Isabelle Hainault
    • , Emilie Montastier
    • , Raphaël G P Denis
    • , Patricia Ancel
    • , Amélie Lacombe
    • , Yin Ling
    • , Omran Allatif
    • , Céline Cruciani-Guglielmacci
    • , Sébastien André
    • , Nathalie Viguerie
    • , Christine Poitou
    • , Vladimir Stich
    • , Alexandra Torcivia
    • , Fabienne Foufelle
    • , Serge Luquet
    • , Judith Aron-Wisnewsky
    • , Dominique Langin
    • , Karine Clément
    • , Irina A Udalova
    •  & Nicolas Venteclef
  • Article |

    Crystal Mackall and colleagues report that antigen-independent signaling of chimeric antigen receptors (CARs) causes T cell exhaustion and reduced therapeutic efficacy of CAR T cells that can be overcome by incorporating the 4-1BB costimulatory domain into the CAR.

    • Adrienne H Long
    • , Waleed M Haso
    • , Jack F Shern
    • , Kelsey M Wanhainen
    • , Meera Murgai
    • , Maria Ingaramo
    • , Jillian P Smith
    • , Alec J Walker
    • , M Eric Kohler
    • , Vikas R Venkateshwara
    • , Rosandra N Kaplan
    • , George H Patterson
    • , Terry J Fry
    • , Rimas J Orentas
    •  & Crystal L Mackall
  • Article |

    The authors uncover new mutations in an enzyme from the purine synthesis pathway that cause resistance to leukemia therapy, and reveal a new mechanism by which they affect drug metabolism.

    • Benshang Li
    • , Hui Li
    • , Yun Bai
    • , Renate Kirschner-Schwabe
    • , Jun J Yang
    • , Yao Chen
    • , Gang Lu
    • , Gannie Tzoneva
    • , Xiaotu Ma
    • , Tongmin Wu
    • , Wenjing Li
    • , Haisong Lu
    • , Lixia Ding
    • , Huanhuan Liang
    • , Xiaohang Huang
    • , Minjun Yang
    • , Lei Jin
    • , Hui Kang
    • , Shuting Chen
    • , Alicia Du
    • , Shuhong Shen
    • , Jianping Ding
    • , Hongzhuan Chen
    • , Jing Chen
    • , Arend von Stackelberg
    • , Longjun Gu
    • , Jinghui Zhang
    • , Adolfo Ferrando
    • , Jingyan Tang
    • , Shengyue Wang
    •  & Bin-Bing S Zhou
  • Article |

    The small molecule Bis-T-23 targets actin polymerization to improve renal morphology and function in several mouse models of kidney injury and disease.

    • Mario Schiffer
    • , Beina Teng
    • , Changkyu Gu
    • , Valentina A Shchedrina
    • , Marina Kasaikina
    • , Vincent A Pham
    • , Nils Hanke
    • , Song Rong
    • , Faikah Gueler
    • , Patricia Schroder
    • , Irini Tossidou
    • , Joon-Keun Park
    • , Lynne Staggs
    • , Hermann Haller
    • , Sergej Erschow
    • , Denise Hilfiker-Kleiner
    • , Changli Wei
    • , Chuang Chen
    • , Nicholas Tardi
    • , Samy Hakroush
    • , Martin K Selig
    • , Aleksandr Vasilyev
    • , Sandra Merscher
    • , Jochen Reiser
    •  & Sanja Sever
  • Article |

    Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection.

    • Laura J Pallett
    • , Upkar S Gill
    • , Alberto Quaglia
    • , Linda V Sinclair
    • , Maria Jover-Cobos
    • , Anna Schurich
    • , Kasha P Singh
    • , Niclas Thomas
    • , Abhishek Das
    • , Antony Chen
    • , Giuseppe Fusai
    • , Antonio Bertoletti
    • , Doreen A Cantrell
    • , Patrick T Kennedy
    • , Nathan A Davies
    • , Muzlifah Haniffa
    •  & Mala K Maini
  • Article |

    The miR-200 family of miRNAs is upregulated in diabetes and leads to the apoptosis of pancreatic beta cells, while its knockout prevents this pathology

    • Bengt-Frederik Belgardt
    • , Kashan Ahmed
    • , Martina Spranger
    • , Mathieu Latreille
    • , Remy Denzler
    • , Nadiia Kondratiuk
    • , Ferdinand von Meyenn
    • , Felipe Nunez Villena
    • , Karolin Herrmanns
    • , Domenico Bosco
    • , Julie Kerr-Conte
    • , Francois Pattou
    • , Thomas Rülicke
    •  & Markus Stoffel
  • Article |

    A high percentage of smooth muscle cells in atherosclerotic lesions lose expression of smooth muscle marker proteins and acquire the phenotype of other cell types, a process of functional importance in lesion pathogenesis that is controlled by the transcription factor KLF4.

    • Laura S Shankman
    • , Delphine Gomez
    • , Olga A Cherepanova
    • , Morgan Salmon
    • , Gabriel F Alencar
    • , Ryan M Haskins
    • , Pamela Swiatlowska
    • , Alexandra A C Newman
    • , Elizabeth S Greene
    • , Adam C Straub
    • , Brant Isakson
    • , Gwendalyn J Randolph
    •  & Gary K Owens
  • Article |

    Cyclophilin A, secreted by bone marrow endothelial cells, acts as a chemotactic factor for myeloma cells, which helps explain their homing to the bone marrow and suggests a potential new therapeutic strategy.

    • Di Zhu
    • , Zhongqiu Wang
    • , Jian-Jun Zhao
    • , Teresa Calimeri
    • , Jiang Meng
    • , Teru Hideshima
    • , Mariateresa Fulciniti
    • , Yue Kang
    • , Scott B Ficarro
    • , Yu-Tzu Tai
    • , Zachary Hunter
    • , Douglas McMilin
    • , Haoxuan Tong
    • , Constantine S Mitsiades
    • , Catherine J Wu
    • , Steven P Treon
    • , David M Dorfman
    • , Geraldine Pinkus
    • , Nikhil C Munshi
    • , Pierfrancesco Tassone
    • , Jarrod A Marto
    • , Kenneth C Anderson
    •  & Ruben D Carrasco
  • Article |

    Metabolic changes induced by hypoxia and extracellular ATP, acting through the transcription factors HIF1-α and AHR, regulate the differentiation of type 1 regulatory (Treg1) cells.

    • Ivan D Mascanfroni
    • , Maisa C Takenaka
    • , Ada Yeste
    • , Bonny Patel
    • , Yan Wu
    • , Jessica E Kenison
    • , Shafiuddin Siddiqui
    • , Alexandre S Basso
    • , Leo E Otterbein
    • , Drew M Pardoll
    • , Fan Pan
    • , Avner Priel
    • , Clary B Clish
    • , Simon C Robson
    •  & Francisco J Quintana

Brief Communication

  • Brief Communication |

    A mutation conferring resistance to novel irreversible EGFR inhibitors is identified in cell-free plasma DNA from lung cancer patients.

    • Kenneth S Thress
    • , Cloud P Paweletz
    • , Enriqueta Felip
    • , Byoung Chul Cho
    • , Daniel Stetson
    • , Brian Dougherty
    • , Zhongwu Lai
    • , Aleksandra Markovets
    • , Ana Vivancos
    • , Yanan Kuang
    • , Dalia Ercan
    • , Sarah E Matthews
    • , Mireille Cantarini
    • , J Carl Barrett
    • , Pasi A Jänne
    •  & Geoffrey R Oxnard
  • Brief Communication |

    The study describes the use of integrative approaches to search for candidate therapeutic targets for DIPG, and the identification of an HDAC inhibitor as a potential treatment strategy

    • Catherine S Grasso
    • , Yujie Tang
    • , Nathalene Truffaux
    • , Noah E Berlow
    • , Lining Liu
    • , Marie-Anne Debily
    • , Michael J Quist
    • , Lara E Davis
    • , Elaine C Huang
    • , Pamelyn J Woo
    • , Anitha Ponnuswami
    • , Spenser Chen
    • , Tessa B Johung
    • , Wenchao Sun
    • , Mari Kogiso
    • , Yuchen Du
    • , Lin Qi
    • , Yulun Huang
    • , Marianne Hütt-Cabezas
    • , Katherine E Warren
    • , Ludivine Le Dret
    • , Paul S Meltzer
    • , Hua Mao
    • , Martha Quezado
    • , Dannis G van Vuurden
    • , Jinu Abraham
    • , Maryam Fouladi
    • , Matthew N Svalina
    • , Nicholas Wang
    • , Cynthia Hawkins
    • , Javad Nazarian
    • , Marta M Alonso
    • , Eric H Raabe
    • , Esther Hulleman
    • , Paul T Spellman
    • , Xiao-Nan Li
    • , Charles Keller
    • , Ranadip Pal
    • , Jacques Grill
    •  & Michelle Monje

Letter

  • Letter |

    Following skin immunization a common naïve T cell precursor gives rise to resident and central memory T cells, which mediate rapid and delayed skin immune responses, respectively.

    • Olivier Gaide
    • , Ryan O Emerson
    • , Xiaodong Jiang
    • , Nicholas Gulati
    • , Suzanne Nizza
    • , Cindy Desmarais
    • , Harlan Robins
    • , James G Krueger
    • , Rachael A Clark
    •  & Thomas S Kupper

News & Views

  • News & Views |

    In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell–mediated immunopathology in hepatitis B virus infection.

    • Silvia Piconese
    •  & Vincenzo Barnaba
  • News & Views |

    Tissue-resident memory T cells (TRM cells) protect against recurrent or renewed infection in barrier tissues such as skin and mucosa. A new study sheds light on the clonal origin of TRM cells and demonstrates a crucial role for tissue-embedded T cell memory in contact hypersensitivity in skin.

    • Thomas Gebhardt
    •  & Francis R Carbone
  • News & Views |

    Atherosclerosis is the primary cause of heart attacks and strokes and is caused by a chronic inflammatory response in the coronary and carotid arteries. A new study shows that smooth muscle cells within atherosclerotic plaques can change phenotypes to become macrophage-like cells, thereby revealing the remarkable plasticity of these cells.

    • Michael E Rosenfeld
  • News & Views |

    A new study identifies recurrent mutations in the purine biosynthesis gene phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in relapsed acute lymphoblastic leukemia (ALL). This work highlights the importance of this pathway in the pathogenesis of relapse and suggests an approach to predicting and circumventing resistance in ALL.

    • Charles G Mullighan

Editorial

  • Editorial |

    Recent news of raids on research budgets illustrates how precarious government funding of scientific research has become. In an era of unprecedented momentum in the development of technologies and therapies for studying and treating disease, opportunities for new discoveries must not be lost due to shortsighted budgetary concerns.

News

News in Brief