Volume 15 Issue 5, May 2014

Volume 15 Issue 5

Treg cells suppress through a variety of mechanisms. Altman and colleagues show that CTLA-4-PKC-η interaction at the Treg cell immunological synapse is required for contact-dependent suppression by Treg cells (p 465; and News and Views by Wülfing, Tunbridge & Wraith, p 408). The original image shows GFP-tagged PKC-η (green) accumulated at the interface between a Treg cell (red) and an antigenpresenting B cell. Cyan indicates the nuclei. Original image by Tadashi Yokosuka and Takashi Saito. Artwork by Lewis Long.

Commentary

News and Views

  • News & Views |

    CTLA-4 is a potent inhibitor of T cell population expansion. The PIX-GIT2-PAK2 complex is recruited to the cytoplasmic domain of CTLA-4 via the kinase PKC-η, which suggests a previously unrecognized aspect of signal transduction via CTLA-4 in immunoregulation.

    • Christoph Wülfing
    • , Helen M Tunbridge
    •  & David C Wraith
  • News & Views |

    Although it is generally considered a proinflammatory cytokine, interleukin 6 (IL-6) has anti-inflammatory effects in macrophages by sensitizing them to IL-4 through upregulation of the IL-4 receptor.

    • Shannon M Reilly
    •  & Alan R Saltiel
  • News & Views |

    Cytokines and other environmental cues influence polarization of CD4+ helper T cells, but the signaling pathways that are involved are less clear. Recent findings show that signaling via an mTORC2-SGK1 kinase axis regulates TH1–TH2 cell-fate polarization.

    • Matthew Norton
    •  & Robert A Screaton

Research Highlights

Review

Articles

  • Article |

    The role of IL-6 in obesity-associated inflammation remains controversial. Bruening and colleagues identify signaling by IL-6 as an important determinant for the alternative activation of macrophages during inflammation.

    • Jan Mauer
    • , Bhagirath Chaurasia
    • , Julia Goldau
    • , Merly C Vogt
    • , Johan Ruud
    • , Khoa D Nguyen
    • , Sebastian Theurich
    • , A Christine Hausen
    • , Joel Schmitz
    • , Hella S Brönneke
    • , Emma Estevez
    • , Tamara L Allen
    • , Andrea Mesaros
    • , Linda Partridge
    • , Mark A Febbraio
    • , Ajay Chawla
    • , F Thomas Wunderlich
    •  & Jens C Brüning
  • Article |

    The function of the lymphocyte-expressed receptor CD96 is almost entirely unknown. Smyth and colleagues demonstrate that it serves a key role in restraining activation of NK cells in part by competing with the activating receptor CD226 (DNAM-1).

    • Christopher J Chan
    • , Ludovic Martinet
    • , Susan Gilfillan
    • , Fernando Souza-Fonseca-Guimaraes
    • , Melvyn T Chow
    • , Liam Town
    • , David S Ritchie
    • , Marco Colonna
    • , Daniel M Andrews
    •  & Mark J Smyth
  • Article |

    Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4+ T cell lineage integrity by repressing Runx-CBFβ complexes in TH1 cells but not in TH2 cells.

    • Nicole Boucheron
    • , Roland Tschismarov
    • , Lisa Göschl
    • , Mirjam A Moser
    • , Sabine Lagger
    • , Shinya Sakaguchi
    • , Mircea Winter
    • , Florian Lenz
    • , Dijana Vitko
    • , Florian P Breitwieser
    • , Lena Müller
    • , Hammad Hassan
    • , Keiryn L Bennett
    • , Jacques Colinge
    • , Wolfgang Schreiner
    • , Takeshi Egawa
    • , Ichiro Taniuchi
    • , Patrick Matthias
    • , Christian Seiser
    •  & Wilfried Ellmeier
  • Article |

    Adaptors of the TRAF family are tumor-necrosis factor receptor–associated factors. So and colleagues show that TRAF5 negative regulates the IL-6 receptor signaling pathway, which limits the induction of proinflammatory CD4+ T cells.

    • Hiroyuki Nagashima
    • , Yuko Okuyama
    • , Atsuko Asao
    • , Takeshi Kawabe
    • , Satoshi Yamaki
    • , Hiroyasu Nakano
    • , Michael Croft
    • , Naoto Ishii
    •  & Takanori So
  • Article |

    The kinase SGK1 is a downstream target of mTORC2 signaling. Powell and colleagues show that SGK1 regulates TH2 polarization by increasing the stability of the transcription factor JunB and antagonizing IFN-γ expression.

    • Emily B Heikamp
    • , Chirag H Patel
    • , Sam Collins
    • , Adam Waickman
    • , Min-Hee Oh
    • , Im-Hong Sun
    • , Peter Illei
    • , Archna Sharma
    • , Aniko Naray-Fejes-Toth
    • , Geza Fejes-Toth
    • , Jyoti Misra-Sen
    • , Maureen R Horton
    •  & Jonathan D Powell
  • Article |

    Signaling events at the Treg cell immune synapse remain unknown. Altman and colleagues show that a CTLA-4–PKC-η signaling axis is required for contact-dependent suppression by Treg cells.

    • Kok-Fai Kong
    • , Guo Fu
    • , Yaoyang Zhang
    • , Tadashi Yokosuka
    • , Javier Casas
    • , Ann J Canonigo-Balancio
    • , Stephane Becart
    • , Gisen Kim
    • , John R Yates III
    • , Mitchell Kronenberg
    • , Takashi Saito
    • , Nicholas R J Gascoigne
    •  & Amnon Altman
  • Article |

    The precise mechanisms of the thymic development Treg cells are still being determined. Farrar and colleagues demonstrate that signals from a triumvirate of members of the tumor-necrosis factor receptor superfamily are critical for Treg cell development in the thymus.

    • Shawn A Mahmud
    • , Luke S Manlove
    • , Heather M Schmitz
    • , Yan Xing
    • , Yanyan Wang
    • , David L Owen
    • , Jason M Schenkel
    • , Jonathan S Boomer
    • , Jonathan M Green
    • , Hideo Yagita
    • , Hongbo Chi
    • , Kristin A Hogquist
    •  & Michael A Farrar