Volume 18 Issue 5, May 2017

Volume 18 Issue 5

The nucleic acid sensor TLR9 needs to be tightly regulated to prevent activation by self-ligands in LAMP1+ endolysosomes. Saveanu and colleagues (p 509) identify the aminopeptidase IRAP as a regulator of endosomal trafficking that reduces spurious TLR9 activation. The original image by Loredana Saveanu depicts confocal microscopy imaging of TLR9–GFP (green) with LAMP1+ endosomes (red) in bone-marrow-derived dendritic cells (blue nuclei stained with DAPI). Artwork by Lewis Long.

Comment

  • Comment |

    Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees.

    • Robyn S Klein
    • , Rhonda Voskuhl
    • , Benjamin M Segal
    • , Bonnie N Dittel
    • , Thomas E Lane
    • , John R Bethea
    • , Monica J Carson
    • , Carol Colton
    • , Susanna Rosi
    • , Aileen Anderson
    • , Laura Piccio
    • , Joan M Goverman
    • , Etty N Benveniste
    • , Melissa A Brown
    • , Seema Kaushalya Tiwari-Woodruff
    • , Tajie H Harris
    •  & Anne H Cross

News and Views

  • News & Views |

    IRE1α is a stress sensor that is activated by a high-fat diet. In adipose-tissue macrophages, it serves as a major switch toward pro-inflammatory M1 polarization and thereby contributes to obesity and associated diseases.

    • Bojan Bujisic
    •  & Fabio Martinon
  • News & Views |

    The immune system employs a multitude of molecules, cells and organs that act together throughout the entire body to guard human health. Much like in a social network, immune cells can exert full functionality only through effective collaboration and communication.

    • Andreas Bergthaler
    •  & Jörg Menche
  • News & Views |

    The transcription factor IRF4 acts as a 'rheostat' for TCR signaling. Discrete levels of IRF4 can activate distinct transcriptional programs in T cells due to binding sites of variable affinity in groups of target genes.

    • Michael P Gallagher
    •  & Leslie J Berg
  • News & Views |

    The short-chain fatty acids (SCFAs) acetate and butyrate, which are released from specialized diets by gut microbes, protect non-obese diabetic (NOD) mice against insulitis and slow the progression of diabetes.

    • Li Wen
    •  & F Susan Wong

Research Highlights

Review

  • Review Article |

    O’Neill and colleagues review the role of mitochondria dynamics and energetics in immunity and inflammation, in innate and adaptive immune cells.

    • Evanna L Mills
    • , Beth Kelly
    •  & Luke A J O'Neill

Articles

  • Article |

    Long noncoding RNAs contribute to the cell-type-specific regulation of gene expression. Fan and colleagues identify a unique conserved lncRNA, lncKdm2b, that is transcribed divergently from the Kdm2b gene and is necessary for ILC3 maintenance in the gut.

    • Benyu Liu
    • , Buqing Ye
    • , Liuliu Yang
    • , Xiaoxiao Zhu
    • , Guanling Huang
    • , Pingping Zhu
    • , Ying Du
    • , Jiayi Wu
    • , Xiwen Qin
    • , Runsheng Chen
    • , Yong Tian
    •  & Zusen Fan
  • Article |

    The receptor TLR9 needs to be carefully regulated to avoid recognition of self nucleic acids and ensuing autoinflammation. Saveanu and colleagues demonstrate a further level of regulation through the retention of TLR9 in IRAP+ endosomes.

    • Joel Babdor
    • , Delphyne Descamps
    • , Aimé Cézaire Adiko
    • , Mira Tohmé
    • , Sophia Maschalidi
    • , Irini Evnouchidou
    • , Luiz Ricardo Vasconcellos
    • , Mariacristina De Luca
    • , Francois-Xavier Mauvais
    • , Meriem Garfa-Traore
    • , Melanie M Brinkmann
    • , Michel Chignard
    • , Bénédicte Manoury
    •  & Loredana Saveanu
  • Article |

    ‘Crown-like’ structures composed of apoptotic adipocytes surrounded by adipose tissue macrophages (ATMs) are a characteristic of obesity. Liu and colleagues show that engulfment of apoptotic adipocytes triggers an ER stress response in ATMs and drives the proinflammatory response that underlies obesity.

    • Bo Shan
    • , Xiaoxia Wang
    • , Ying Wu
    • , Chi Xu
    • , Zhixiong Xia
    • , Jianli Dai
    • , Mengle Shao
    • , Feng Zhao
    • , Shengqi He
    • , Liu Yang
    • , Mingliang Zhang
    • , Fajun Nan
    • , Jia Li
    • , Jianmiao Liu
    • , Jianfeng Liu
    • , Weiping Jia
    • , Yifu Qiu
    • , Baoliang Song
    • , Jing-Dong J Han
    • , Liangyou Rui
    • , Sheng-Zhong Duan
    •  & Yong Liu
  • Article |

    The intracellular sensor NLRP12 can negatively regulate inflammation. Ting and colleagues demonstrate that an absence of NLRP12 triggers a dysbiosis that feeds forward into a process of inflammation and colitis.

    • Liang Chen
    • , Justin E Wilson
    • , Mark J Koenigsknecht
    • , Wei-Chun Chou
    • , Stephanie A Montgomery
    • , Agnieszka D Truax
    • , W June Brickey
    • , Christopher D Packey
    • , Nitsan Maharshak
    • , Glenn K Matsushima
    • , Scott E Plevy
    • , Vincent B Young
    • , R Balfour Sartor
    •  & Jenny P-Y Ting
  • Article |

    The gut microbiota can influence immune-cell function by the production of short-chain fatty acids. Mackay and colleagues show that diets enriched for acetate and butyrate protect non-obese diabetic mice from insulitis and diabetes progression.

    • Eliana Mariño
    • , James L Richards
    • , Keiran H McLeod
    • , Dragana Stanley
    • , Yu Anne Yap
    • , Jacinta Knight
    • , Craig McKenzie
    • , Jan Kranich
    • , Ana Carolina Oliveira
    • , Fernando J Rossello
    • , Balasubramanian Krishnamurthy
    • , Christian M Nefzger
    • , Laurence Macia
    • , Alison Thorburn
    • , Alan G Baxter
    • , Grant Morahan
    • , Lee H Wong
    • , Jose M Polo
    • , Robert J Moore
    • , Trevor J Lockett
    • , Julie M Clarke
    • , David L Topping
    • , Leonard C Harrison
    •  & Charles R Mackay
  • Article |

    Murphy and colleagues show that the transcription-factor complex BATF-IRF4, which recognizes AICE motifs within gene enhancers, is sensitive to TCR signaling strength and identify distinct gene targets that respond to graded doses of TCR stimulation.

    • Arifumi Iwata
    • , Vivek Durai
    • , Roxane Tussiwand
    • , Carlos G Briseño
    • , Xiaodi Wu
    • , Gary E Grajales-Reyes
    • , Takeshi Egawa
    • , Theresa L Murphy
    •  & Kenneth M Murphy
  • Article |

    Distinct transcription factors influence cell fate, including the generation of effector or memory CD8+ T cells. Goldrath, Wang and colleagues have developed a Page-Rank analysis that shows that the transcription factors YY1 and Nr3c1, which are expressed constitutively, promote the differentiation of effector cells or memory cells, respectively.

    • Bingfei Yu
    • , Kai Zhang
    • , J Justin Milner
    • , Clara Toma
    • , Runqiang Chen
    • , James P Scott-Browne
    • , Renata M Pereira
    • , Shane Crotty
    • , John T Chang
    • , Matthew E Pipkin
    • , Wei Wang
    •  & Ananda W Goldrath

Resource

  • Resource |

    Immune cells give rise to the most interconnected system in the body. Meissner and colleagues perform comprehensive proteomics and secretomics to describe in detail the ‘social network’ of human immune cells and throw light on previously unknown cell connectivities.

    • Jan C Rieckmann
    • , Roger Geiger
    • , Daniel Hornburg
    • , Tobias Wolf
    • , Ksenya Kveler
    • , David Jarrossay
    • , Federica Sallusto
    • , Shai S Shen-Orr
    • , Antonio Lanzavecchia
    • , Matthias Mann
    •  & Felix Meissner