News & Views

  • News & Views |

    Single-cell-sequencing techniques enable the decades-old T helper subset dogma to be re-examined in an unsupervised manner, bringing nuance to the definition of known subsets while simultaneously identifying interesting new cell states.

    • Jasper J. P. van Beek
    • , Maria Rescigno
    •  & Enrico Lugli
  • News & Views |

    A new study shows successful immunotherapy of a detrimental gastrointestinal disease using the complement inhibitor eculizumab.

    • Chack-Yung Yu
    •  & Stacy P. Ardoin
  • News & Views |

    Following internalization of an actin-bearing ligand, the C-type lectin receptor DNGR-1 promotes phagosome rupture, allowing antigens to access the cytosol and be processed through the MHC-I pathway.

    • Remi Hatinguais
    •  & Gordon D. Brown
  • News & Views |

    Comprehensive analysis of specific and cross-reactive SARS-CoV-2 epitopes reveals functional T cell responses against specific viral regions in essentially all convalescent individuals and a majority of unexposed donors, demonstrating that cross-reactive responses to COVID-19 are widespread.

    • André Perez-Potti
    • , Joshua Lange
    •  & Marcus Buggert
  • News & Views |

    The natural variability of CRELD1 expression identified in comprehensive data sets from healthy individuals helps predict and establish its role in regulating T cell homeostasis.

    • Fotini Gounari
  • News & Views |

    A subset of neutrophils with an immature phenotype confers neuroprotection in traumatic optic nerve and spinal cord injury. This study identifies a new target population of cells for therapeutic strategies to induce neural regeneration during injury.

    • Rhonda Voskuhl
  • News & Views |

    An exaggerated extrafollicular B cell response characteristic of active systemic lupus erythematosus also characterizes the B cell response to SARS-CoV-2 in those with severe COVID-19.

    • A. Darise Farris
    •  & Joel M. Guthridge
  • News & Views |

    The presence of central memory precursor cells during the acute response to cytomegalovirus infection is the best predictor of whether a T cell family will contribute to the inflationary memory pool.

    • Matthew A. Huggins
    •  & Sara E. Hamilton
  • News & Views |

    In contrast with the classical dogma that the pathways generating either memory or ‘exhausted’ T cells are strictly segregated, data now identify a clonally distinct hybrid memory T cell subpopulation with an exhausted phenotype.

    • Talyn Chu
    • , Jacqueline Berner
    •  & Dietmar Zehn
  • News & Views |

    The lung endothelial cell–derived angiocrine Rspondin3 activates Wnt–β-catenin signaling in interstitial macrophages, leading to a metabolic–epigenetic reprogramming of interstitial macrophages that drives anti-inflammatory responses and attenuates endotoxin-induced lung injury.

    • Thomas Marichal
  • News & Views |

    Two studies reveal a role for the transcriptional regulator BATF3 as a T cell–intrinsic factor mediating effective memory responses. This finding opens future avenues of investigation and opportunities to enhance cellular immunotherapy.

    • Caleb A. Lareau
    •  & Ansuman T. Satpathy
  • News & Views |

    The mechanisms that drive responses to PD-1-blocking immunotherapy in some but not all patients have been puzzling. A new study suggests that the balance of PD-1 expression levels between CD8+ T cells and Treg cells might provide an answer.

    • Halil-Ibrahim Aksoylar
    •  & Vassiliki A. Boussiotis
  • News & Views |

    The activation of the Notch4–Wnt–GDF15 axis in induced regulatory T (Treg cells) dampens their immunoregulatory function and turns them into TH2 and TH17 cytokine producers, allowing them to maintain ongoing allergic asthma.

    • Hamida Hammad
    •  & Bart N. Lambrecht
  • News & Views |

    Cytokines are well-known mediators of the immune response, but, recently, pleiotropic roles in the central nervous system have started to be uncovered. It is now shown that IL-17 directly modulates fear behavior in mice.

    • Rejane Rua
    •  & Nathalie Pujol
  • News & Views |

    Comprehensive mapping reveals that functional CD4+ and CD8+ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response.

    • Leo Swadling
    •  & Mala K. Maini
  • News & Views |

    Costimulatory blockade via the CTLA-4–Ig fusion protein abatacept is beneficial in patients with early-onset type 1 diabetes, but some individuals benefit more than others. A new study reports that the pretreatment abundance of T follicular helper (TFH) cells could predict clinical responses to abatacept.

    • Estelle Bettelli
    •  & Daniel J. Campbell
  • News & Views |

    To trigger an adequate humoral immune response while ensuring self-tolerance, B cell activation is tightly controlled. A new study indicates that an NR4A-enforced built-in brake fine-tunes the early phase of transcriptional reprogramming induced by BCR stimulation.

    • Louisa Hill
    •  & Tanja A. Schwickert
  • News & Views |

    A vicious cycle, linking obesity with chronic inflammation, fuels the development and exacerbation of metabolic syndrome and other disorders. Modulation of mitochondrial energy metabolism via interleukin-1β signaling establishes a runaway positive-feedback loop that brings about and reinforces the sequelae of a high-fat diet.

    • Nektarios Tavernarakis
  • News & Views |

    New studies suggest that NKG7 is essential for NK and CD8+ T cell cytotoxic degranulation and CD4+ T cell activation and proinflammatory responses. While the mechanism is yet to be determined, the functional relevance is exciting and opens the possibility of a new target for cellular immunotherapies.

    • Subramaniam Malarkannan
  • News & Views |

    The combination of single-cell RNA-seq and in vivo CRISPR–Cas9 screens reveal a new circuit that directs germinal center B cells toward a memory B cell phenotype during viral infection.

    • Kim L. Good-Jacobson
    •  & Joanna R. Groom
  • News & Views |

    Group 2 innate lymphoid cells (ILC2s) closely intersect with antitumor immunity. A new study describes how activation of lung-resident ILC2s orchestrates the suppression of natural killer cell–mediated innate antitumor immunity via an eosinophil-mediated metabolic mechanism.

    • Haiming Wei
    •  & Binqing Fu
  • News & Views |

    Durable responses to immunotherapy require the development of robust CD8+ T cell memory. A new study indicates that NRP1 differs from other checkpoint receptors as it functions as a checkpoint for the generation of memory.

    • Nandini Acharya
    •  & Ana C. Anderson
  • News & Views |

    A complex formed by the chemokine CXCL10 and commensal skin microbiota–derived DNA is a crucial component that triggers type I IFN responses to facilitate skin repair.

    • Vinod Nadella
    •  & Keisuke Nagao
  • News & Views |

    Guanylate-binding proteins (GBPs) promote immune defenses against infectious agents. Two studies reveal that GBP1 directly binds to cytosolic lipopolysaccharide (LPS), bringing caspase-4 to the surface of bacteria to induce pyroptosis.

    • Shouya Feng
    •  & Si Ming Man
  • News & Views |

    Antigen escape by solid tumors has limited the efficacy of genetically modified T cells. T cells engineered to secrete the cytokine Flt3L induce the activation of endogenous T cells, enabling a broader repertoire of tumor antigens to be targeted via the expansion of intratumoral antigen presenting cells, significantly improving tumor responses.

    • Emma C. Morris
  • News & Views |

    CAR T cells are engineered to recognize tumor-specific antigens and kill tumor cells. A study of CAR T cell activation using single-molecule microscopy reveals that CARs fail to efficiently convert antigen binding into early T cell signaling events.

    • Björn F. Lillemeier
  • News & Views |

    Quantitative systems-level proteomics is cleverly used to reveal a dynamic program of protein turnover in naive and memory CD4+ T cells that, alongside a stockpile of metabolic protein machinery, poises the cells for activation.

    • Julia M. Marchingo
    •  & Doreen A. Cantrell
  • News & Views |

    Evolutionary genetic and experimental analyses suggest that mutations causing familial Mediterranean fever have been positively selected in the Middle East, probably because they confer heightened resistance against Yersinia pestis infection.

    • Etienne Patin
  • News & Views |

    CXCR3+ regulatory T cells, known to limit type 1 immune responses, can promote tissue-resident immunity by providing bioactive transforming growth factor-β to CD8+ T cells.

    • Nicole Joller
  • News & Views |

    Caspase-cleaved gasdermin D forms pores in cellular membranes, thus executing proinflammatory cell death by pyroptosis. Disulfiram — a drug used to treat chronic alcoholism — is now found to be an inhibitor of pore formation, which may therapeutically counteract exacerbated inflammation in sepsis and beyond.

    • Florian I. Schmidt
    •  & Eicke Latz
  • News & Views |

    The identification of the acute phase protein serum amyloid A as a soluble allergen sensor sheds new light on the mechanisms involved in the induction of type II airway inflammation.

    • Rudi W. Hendriks
  • News & Views |

    A new report finds that peripheral immunization generates tissue-resident memory CD8+ T cells in the central nervous system that provide robust protection against local infection.

    • Michael A. Kovacs
    •  & Tajie H. Harris
  • 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
  • News & Views |

    B cells undergo iterative rounds of somatic hypermutation and selection for high-affinity antigen binding in the germinal center microenvironment. Two new studies provide insights into the temporal and spatial control mechanisms that act within B cells and follicular dendritic cells to jointly govern B cell differentiation and cell traffic within the GC.

    • Jagan R. Muppidi
    •  & Ulf Klein
  • News & Views |

    Injury or infection renders patients vulnerable to secondary pneumonia. A new study indicates that SIRP-α triggers prolonged impairment of the phagocytic capacity of alveolar macrophages after the resolution of primary bacterial or viral pneumonia.

    • Alex F. de Vos
    •  & Tom van der Poll
  • News & Views |

    Myeloid-derived suppressor cells (MDSCs) occupy sites of chronic inflammation and suppress CD8+ T cell function. A new study describes the transfer of the metabolite methylglyoxal (MG) to T cells, which mediates this immunosuppressive mechanism.

    • Vijyendra Ramesh
    •  & Jason W. Locasale
  • News & Views |

    Single-cell RNA-sequencing of myeloid cells during neuroinflammation identifies a new population of pathogenic Cxcl10-expressing phagocytes, which develop independently of Ly6Chi monocytes but derive from early myeloid precursors shaped by the inflamed tissue microenvironment.

    • Burkhard Becher
    • , Donatella De Feo
    • , Ana Amorim
    •  & Melanie Greter
  • News & Views |

    Activation of TLR–TRAF6 signaling by chronic inflammation in myelodysplastic syndromes increases the competitive advantage of HSPCs harboring MDS mutations through the upregulation of the ubiquitin-modifying enzyme A20 and a switch from canonical to non-canonical NF-κB signaling.

    • Koki Ueda
    • , Rajni Kumari
    •  & Ulrich Steidl
  • News & Views |

    Oxidative stress is an imbalance in the production of reactive oxygen species and the ability to remove or detoxify these molecules, which causes cellular damage. Leveraging novel sequencing methods and high-throughput screens leads to the discovery of possible new therapies.

    • Shane A. Liddelow
  • News & Views |

    CD8 memory–phenotype differentiation is a T cell antigen receptor–governed process that begins in Eomes+ thymic precursors and is subsequently completed in the periphery. These CD8-MP cells can infiltrate tumors, where they express PD-1.

    • Mark A. Daniels
    •  & Emma Teixeiro
  • News & Views |

    Epigenetic modifications are associated with distinct stages of autoreactive CD8+ T cell differentiation. DNA methylation and chromatin changes guide the acquisition of a memory-like phenotype and sustain prolonged autoimmune effector responses.

    • Luca Petiti
    •  & Luigia Pace
  • 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
  • News & Views |

    Comprehensive analysis of CD8+ T cell populations specific to cytomegalovirus reveals that the evolution of the T cell antigen receptor repertoire during chronic infections is characterized by the expansion of low-affinity clones.

    • Anke Redeker
    •  & Ramon Arens
  • News & Views |

    The ubiquitin-editing enzyme A20 has a pivotal role in restricting autoimmune and inflammatory responses. New studies suggest that A20 prevents inflammatory diseases using a non-catalytic mechanism involving ubiquitin binding.

    • Shao-Cong Sun
  • News & Views |

    Chronic inflammation associated with HIV-1 infection disrupts the homeostasis of gut-resident innate lymphoid cells and induces the generation and expansion of adaptive NK cells expressing TCF7, a transcription factor that sustains their effector functions and memory-like properties.

    • Joanna Mikulak
    • , Clara Di Vito
    •  & Domenico Mavilio
  • News & Views |

    Regulatory T (Treg) cells suppress antitumor immunity, but Treg cell inhibition has been hampered by a lack of specific targets. CD36 expression by tumor-infiltrating Treg cells may provide a way to specifically target Treg cells in tumors.

    • Brendan L. Horton
    •  & Stefani Spranger