Biochemistry articles within Nature Immunology

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  • News & Views |

    The microbiome is known to affect antitumor immune responses, but how this occurs is unclear. Rhamnose-rich polysaccharides (RHP) from a commensal strain of Lactiplantibacillus plantarum have now been shown to induce iron sequestration by tumor macrophages, thereby limiting tumor growth and promoting antitumor immunity.

    • Samuel P. Nobs
    •  & Eran Elinav

  • News & Views |

    MEF2C is a transcription factor that has known functions in a variety of cell types, but it has not yet been ascribed a role in natural killer cells. Data now show that MEF2C promotes the functional responses of human and murine natural killer cells by controlling their metabolic programs.

    • Pamela Wong
    •  & Todd A. Fehniger

  • Article
    | Open Access

    Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.

    • Hannah F. Bradford
    • , Thomas C. R. McDonnell
    •  & Claudia Mauri

  • News & Views |

    Visceral adipose tissue hosts at least two populations of mature FOXP3+ regulatory T cells, which together can preserve systemic metabolism and control inflammation.

    • Melanie Grusdat
    •  & Dirk Brenner

  • News & Views |

    Intratumoral regulatory T (Treg) cells can suppress antitumor immunity. Unlike in splenic Treg cells, the H3K9me2 demethylase JMDJ1 seems to be induced, and is required for this function, in the tumor microenvironment, and targeting it with a small-molecule inhibitor can suppress tumor growth in mice.

    • Xuezheng Wang
    •  & Keji Zhao

  • Article |

    Here, the authors characterize two distinct Treg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2+ Treg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3+ Treg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.

    • Santiago Valle Torres
    • , Kevin Man
    •  & Axel Kallies

  • News & Views |

    Apart from lifestyle, environment and chance events, genetic factors have a key role in delineating the health and longevity of an individual. Research by Park et al. has now shed light on the role of mammalian GIMAP5, a longevity-assurance (LASS) gene encoding a GTP-binding protein that regulates ceramide synthesis and cellular senescence.

    • Atrayee Gope
    •  & Claudio Mauro

  • Article |

    Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

    • Ann Y. Park
    • , Michael Leney-Greene
    •  & Michael J. Lenardo

  • Review Article |

    Bantug and Hess discuss the metabolic interplay between tumor-resident cells and how the effect of metabolism-targeted anticancer strategies on non-transformed or immune cells in the tumor needs to be considered.

    • Glenn R. Bantug
    •  & Christoph Hess

  • Article
    | Open Access

    Unlike metabolic reprogramming that is characteristic of macrophage inflammatory polarization responses to lipopolysaccharide and TLR4 stimulation, the metabolism underlying inflammatory responses to CD40 signaling is not well characterized. Here the authors show CD40 signaling drives fatty acid oxidation and glutamine metabolism resulting in regulation of the NAD+/NADH ratio, which in turn promotes antitumor and pro-inflammatory macrophage functions.

    • Pu-Ste Liu
    • , Yi-Ting Chen
    •  & Ping-Chih Ho

  • News & Views |

    A specialized subset of iNKT cells populates the skin in early life, where their supply of transferrin regulates iron metabolism to promote hair follicle development.

    • Hui-Fern Koay
    •  & Laura K. Mackay

  • Research Highlight |

    • Laurie A. Dempsey

  • Review Article |

    Godbout and colleagues discuss the neuroimmune mechanisms that underlie social-stress defeat, anxiety, and post-traumatic stress disorder.

    • Rebecca G. Biltz
    • , Caroline M. Sawicki
    •  & Jonathan P. Godbout

  • News & Views |

    Lymphocyte activation gene 3 (LAG3) is an important checkpoint inhibitor molecule of immunotherapeutic interest. New crystal structures of LAG3 provide important insight into its molecular architecture, laying the groundwork for future basic and applied investigations.

    • Jan Petersen
    •  & Jamie Rossjohn

  • News & Views |

    Inflamed tissue has a special milieu, with hypoxia, high levels of metabolites from anaerobic glycolysis, and acidosis. Stimulation of a proton-activated receptor, TDAG8 (GPR65), in T cells has an important role in inflammatory bowel disease by balancing pro- and anti-inflammatory signals.

    • Carsten A. Wagner
    •  & Pedro H. Imenez Silva

  • Review Article |

    The transcription factor TCF-1 has multiple roles during T cell development and in mature T cells. Gounari and Khazaie review the potential mechanisms by which TCF-1 regulates gene expression.

    • Fotini Gounari
    •  & Khashayarsha Khazaie

  • Meeting Report |

    On 15–16 November 2021, the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI) and the National Heart, Lung, and Blood Institute (NHLBI) hosted a virtual workshop on DEAD/DEAH-box RNA helicases in health and disease. The goal of the workshop was to review current advances, and identify knowledge gaps and future research to improve our understanding of the function of RNA helicases, and leverage these molecules as molecular targets with translational potential.

    • Ourania Andrisani
    • , Qian Liu
    •  & Michael Gale Jr

  • News & Views |

    Zhong et al. exploit allelic variations in mice to pinpoint the ‘heavy lifter’ transcription factor families governing the chromatin landscape of resting and activated T cells.

    • Timothy M. Johanson
    •  & Rhys S. Allan

  • Letter
    | Open Access

    ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.

    • Laura Surace
    • , Jean-Marc Doisne
    •  & James P. Di Santo

  • News & Views |

    New reports provide further insight into the role of the transcription factor BATF in pivoting the differentiation of CD8+ T cells away from T cell exhaustion and facilitating the transition of these cells into potent effectors.

    • Shannon K. Boi
    • , Xin Lan
    •  & Ben Youngblood

  • News & Views |

    Long-term pathogen and tumor control as well as checkpoint immunotherapies rely on ‘stem-like’ CD8+ T cells. New results uncover BACH2 as a key regulator of this subpopulation and solve an important piece of the puzzle.

    • Lara Labarta-Bajo
    •  & Elina I. Zúñiga

  • Comment |

    Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during TH1 and TH2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her lab showed that differentiated TH1 and TH2 cells, which produce the cytokines IFN-γ and IL-4, respectively, displayed distinct patterns of DNase I hypersensitivity, histone acetylation and NFAT1 transcription factor binding around the Ifng and Il4 genes. This project turned them into a ‘real’ immunology lab!

    • Anjana Rao

  • News & Views |

    Host cell cholesterol is often exploited by pathogens for entry and egress. Two new studies elucidate a new interferon-inducible mechanism by which cells limit plasma membrane cholesterol to promote antibacterial defense.

    • Eric V. Dang
    • , Hiten D. Madhani
    •  & Russell E. Vance

  • Article |

    Bensinger and colleagues show that interferons promote host cell resistance to bacterial cytolysins by decreasing cholesterol synthesis and promoting the esterification of cholesterol, which alters the availability of this pool of ‘free’ cholesterol needed for pore formation.

    • Quan D. Zhou
    • , Xun Chi
    •  & Steven J. Bensinger

  • Comment |

    Immunologists used to avoid metabolism, but that is no longer possible. Now that we must talk about it, how can we do so in a way that enhances and clarifies our understanding of the role metabolism plays in the immune response?

    • Michael P. Murphy
    •  & Luke A. J. O’Neill

  • News & Views |

    γδ T cells are critical contributors to tissue homeostasis. Recent research identifies an unexpected role for γδ T cell–derived IL-17F in promoting sympathetic innervation and tissue thermogenesis through the induction of the cytokine TGF-β in adipose cells.

    • Maria Ciofani

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