Volume 17 Issue 4, April 2016

Volume 17 Issue 4

Langerhans cells and tissue-resident memory CD8+ T cells require an active form of the cytokine TGF-β. Kaplan and colleagues (p 414) demonstrate that specific integrins expressed by epithelial cells activate latent TGF-β and that this is critical for maintaining resident immune cells in the skin and gut. The original image by Javed Mohammed shows epidermal whole mounts from mice doubly-deficient in the integrins β6 and β8 stained for the alloantigen Thy-1.1 (red) and MHC class II (green) after infection with LCMV. Artwork by Lewis Long.

Correspondence

News and Views

  • News & Views |

    The detection of cytosolic DNA by the sensor cGAS triggers potent antiviral responses. New data now propose that cGAS is regulated on a post-translational level by glutamylation.

    • Andrea Ablasser
  • News & Views |

    The accumulation of intestinal Foxp3+ regulatory T cells (Treg cells) in response to the microbiota is tightly regulated. Epithelial apoptosis inhibits the production of tolerogenic interferon-β by myeloid cells and thereby reduces the frequency of Treg cells and lowers the threshold for inflammatory responses.

    • Johanna Pott
    • , Kevin J Maloy
    •  & Ana Izcue
  • News & Views |

    Single-cell RNA sequencing of human innate lymphoid cells (ILCs) reveals conserved transcriptional programs and defines previously unappreciated heterogeneity. These findings pave the way for future investigation of the function and therapeutic potential of ILCs in human health and disease.

    • Gregory F Sonnenberg
  • News & Views |

    The silencing of autoreactive immature B cells is regulated by the binding of self antigens to B cell antigen receptors. New findings show that microRNAs control mechanisms of B cell tolerance.

    • Eric Meffre

Research Highlights

Review

  • Review Article |

    Control of infection depends on the efficient coordination of responses by various cell populations of the immune system. Gause and colleagues review the interactions between cells of the innate immune system and stroma that enable effective responses to invading pathogens.

    • Amariliz Rivera
    • , Mark C Siracusa
    • , George S Yap
    •  & William C Gause

Perspective

Articles

  • Article |

    Van Heijst and colleagues show that CD4+ T cells are programmed to downregulate TCR expression at the peak of clonal expansion in proportion to the strength of initial antigen recognition.

    • Alena M Gallegos
    • , Huizhong Xiong
    • , Ingrid M Leiner
    • , Bože Sušac
    • , Michael S Glickman
    • , Eric G Pamer
    •  & Jeroen W J van Heijst
  • Article |

    Activation of NK cells by hematopoietic targets is controlled by the SLAM receptors and SAP adaptors. Veillette and colleagues show that SLAM-SAP pathways also control NK cell cytotoxicity against nonhematopoietic targets through SLAMF6 homotypic interactions and education.

    • Ning Wu
    • , Ming-Chao Zhong
    • , Romain Roncagalli
    • , Luis-Alberto Pérez-Quintero
    • , Huaijian Guo
    • , Zhanguang Zhang
    • , Christelle Lenoir
    • , Zhongjun Dong
    • , Sylvain Latour
    •  & André Veillette
  • Article |

    Type I interferons suppress viral infection. Ge and colleagues show that the kinase CK1ɛ contributes to this innate immune response by phosphorylating the signaling adaptor TRAF3 to facilitate the expression of type I interferons.

    • Yilong Zhou
    • , Chenxi He
    • , Dapeng Yan
    • , Feng Liu
    • , Haipeng Liu
    • , Jianxia Chen
    • , Ting Cao
    • , Mianyong Zuo
    • , Peng Wang
    • , Yan Ge
    • , Haojie Lu
    • , Qinghe Tong
    • , Chengfeng Qin
    • , Yongqiang Deng
    •  & Baoxue Ge
  • Article |

    Sepsis is poorly understood, largely untreatable and frequently fatal. Netea and colleagues assess both mouse sepsis and human sepsis to demonstrate that its late phase is characterized by immunoparalysis and broad metabolic alterations in cells of the immune system.

    • Shih-Chin Cheng
    • , Brendon P Scicluna
    • , Rob J W Arts
    • , Mark S Gresnigt
    • , Ekta Lachmandas
    • , Evangelos J Giamarellos-Bourboulis
    • , Matthijs Kox
    • , Ganesh R Manjeri
    • , Jori A L Wagenaars
    • , Olaf L Cremer
    • , Jenneke Leentjens
    • , Anne J van der Meer
    • , Frank L van de Veerdonk
    • , Marc J Bonten
    • , Marcus J Schultz
    • , Peter H G M Willems
    • , Peter Pickkers
    • , Leo A B Joosten
    • , Tom van der Poll
    •  & Mihai G Netea
  • Article |

    The cytokine TGF-β maintains the residency of cells of the immune system in barrier tissues. Kaplan and colleagues demonstrate that specific integrins expressed by epithelial cells activate latent TGF-β and that this is critical to maintain residency of cells of the immune system in the skin and gut.

    • Javed Mohammed
    • , Lalit K Beura
    • , Aleh Bobr
    • , Brian Astry
    • , Brian Chicoine
    • , Sakeen W Kashem
    • , Nathan E Welty
    • , Botond Z Igyártó
    • , Sathi Wijeyesinghe
    • , Emily A Thompson
    • , Catherine Matte
    • , Laurent Bartholin
    • , Alesia Kaplan
    • , Dean Sheppard
    • , Alina G Bridges
    • , Warren D Shlomchik
    • , David Masopust
    •  & Daniel H Kaplan
  • Article |

    Using genetic approaches and transcriptional profiling, Kallies and colleagues reveal a common program of effector CD8+ T cell differentiation that is regulated by the cooperation of IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet.

    • Annie Xin
    • , Frederick Masson
    • , Yang Liao
    • , Simon Preston
    • , Tianxia Guan
    • , Renee Gloury
    • , Moshe Olshansky
    • , Jian-Xin Lin
    • , Peng Li
    • , Terence P Speed
    • , Gordon K Smyth
    • , Matthias Ernst
    • , Warren J Leonard
    • , Marc Pellegrini
    • , Susan M Kaech
    • , Stephen L Nutt
    • , Wei Shi
    • , Gabrielle T Belz
    •  & Axel Kallies
  • Article |

    Immature self-reactive B cells undergo central tolerance as they emerge from the bone marrow. Xiao and colleagues show that B cell tolerance requires downregulation of the microRNA miR-148a, as aberrant expression of miR-148a increases survival of autoreactive B cells and contributes to autoimmunity.

    • Alicia Gonzalez-Martin
    • , Brian D Adams
    • , Maoyi Lai
    • , Jovan Shepherd
    • , Maria Salvador-Bernaldez
    • , Jesus M Salvador
    • , Jun Lu
    • , David Nemazee
    •  & Changchun Xiao
  • Article |

    Epithelia continually undergo apoptosis, but the physiological importance of this is unclear. Shibuya and colleagues show that apoptotic epithelial cells bind the glycoprotein CD300a on a dendritic cell subset at barrier surfaces and this negatively regulates commensal-driven Treg cell proliferation.

    • Chigusa Nakahashi-Oda
    • , Kankanam Gamage Sanath Udayanga
    • , Yoshiyuki Nakamura
    • , Yuta Nakazawa
    • , Naoya Totsuka
    • , Haruka Miki
    • , Shuichi Iino
    • , Satoko Tahara-Hanaoka
    • , Shin-ichiro Honda
    • , Kazuko Shibuya
    •  & Akira Shibuya

Resources

  • Resource |

    Several populations of innate lymphoid cells have been identified by their cytokine and transcription factor expression. Mjösberg and colleagues report considerable heterogeneity within human tonsil innate lymphoid cell subpopulations, as revealed by single-cell RNA-sequencing profiling.

    • Åsa K Björklund
    • , Marianne Forkel
    • , Simone Picelli
    • , Viktoria Konya
    • , Jakob Theorell
    • , Danielle Friberg
    • , Rickard Sandberg
    •  & Jenny Mjösberg
  • Resource |

    Using a systems-biology approach, Liston and colleagues profile the immune system of 670 healthy volunteers to provide a description of the population-level heterogeneity in the cellular composition of the circulating immune system.

    • Edward J Carr
    • , James Dooley
    • , Josselyn E Garcia-Perez
    • , Vasiliki Lagou
    • , James C Lee
    • , Carine Wouters
    • , Isabelle Meyts
    • , An Goris
    • , Guy Boeckxstaens
    • , Michelle A Linterman
    •  & Adrian Liston

Corrigenda

Errata