Immunology articles within Nature Communications

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  • Article
    | Open Access

    CD226 is an activating receptor expressed in a co-varied manner with inhibitory receptors on natural killer (NK) cells, but whether CD226 is involved in NK cell education is unclear. Here the authors show that CD226 expression is plastic depending on the MHC environment and endows educated NK cells enhanced effector functions.

    • Arnika K. Wagner
    • , Nadir Kadri
    •  & Benedict J. Chambers

  • Article
    | Open Access

    NOTCH signalling stimulates oligodendrocyte progenitor cell proliferation but how this regulates demyelinating disease is unclear. Here, the authors show that an IL-17 adaptor protein, Act1, interacts with the C-terminal fragment of NOTCH1 (NICD) to activate cell proliferation and an inflammatory response.

    • Chenhui Wang
    • , Cun-Jin Zhang
    •  & Xiaoxia Li

  • Article
    | Open Access

    T helper 17 (Th17) cells can be pathogenic, but what controls this phenotype is unclear. Here the authors show that the transcription factor JunB promotes proinflammatory Th17 function by regulating the transcription of multiple Th17-related genes.

    • Zafrul Hasan
    • , Shin-ichi Koizumi
    •  & Hiroki Ishikawa

  • Article
    | Open Access

    Glucose is an important nutrient that feeds into glycolytic control of T cell function and differentiation. Here the authors show that T cells are superior to dendritic cells (DC) at glucose uptake, and by depriving DCs of this nutrient in their microenvironment T cells activate DC proinflammatory functions, which in turn enhance T cell effector functions in DC-T cell cocultures.

    • Simon J. Lawless
    • , Nidhi Kedia-Mehta
    •  & David K. Finlay

  • Article
    | Open Access

    B cell development involves sequential rearrangement of the immunoglobulin chains, but fine control over the selection process remains a mystery. Here the authors show that individual alleles in pre-B cells are clonally unique and result from stochastic activation of V gene segments to induce optimal generation of a diverse repertoire.

    • Rena Levin-Klein
    • , Shira Fraenkel
    •  & Yehudit Bergman

  • Article
    | Open Access

    There are few methods available that can quantify relationships between cell types in tissue images. Here the authors present a quantitative method to evaluate cellular organization, validated in the mouse thymus and spinal cord, called Multitaper Circularly Averaged Spectral Analysis (MiCASA).

    • Andrew Sornborger
    • , Jie Li
    •  & Nancy R. Manley

  • Article
    | Open Access

    The binding of the leukocyte integrin Mac1 to the platelet receptor GPIbα is important for the physiological response to tissue injury. Here the authors show that this interaction also regulates thrombosis, without influencing bleeding time, which may provide clues for the development of new anti-thrombotic drugs.

    • Yunmei Wang
    • , Huiyun Gao
    •  & Daniel I. Simon

  • Article
    | Open Access

    Thrombospondin-1 (TSP-1) activates latent TGF-β in the extracellular matrix. Here the authors show that inappropriate activation of latent TGF-β in murine, bovine and human lung by monocyte-produced TSP-1 causes pulmonary hypertension, and that interference with the activation process prevents disease development.

    • Rahul Kumar
    • , Claudia Mickael
    •  & Brian B. Graham

  • Article
    | Open Access

    Viruses trigger potent cytotoxic T cell responses, whereas anti-tumour immunity has been difficult to establish. Here the authors engineer a replicating viral delivery system for tumour-associated antigens, which induces alarmin release, innate activation and protective anti-tumour immunity in mice.

    • Sandra M. Kallert
    • , Stephanie Darbre
    •  & Daniel D. Pinschewer

  • Article
    | Open Access

    D-glutamate is an essential component of the bacterial cell wall. Here, the authors use mouse models of infection withAcinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureusto show that bacterial mutants unable to synthesize D-glutamate can potentially be used as live attenuated vaccines.

    • Maria P. Cabral
    • , Patricia García
    •  & Germán Bou

  • Article
    | Open Access

    The role of long noncoding RNAs in regulating T-cell differentiation within the tumour microenvironment is unclear. Here the authors identify a lncRNA that, through direct interactions with EGFR, promotes T-regulatory cell differentiation within the microenvironment of hepatocellular carcinoma, thus promoting tumour growth via immune suppression.

    • Runqiu Jiang
    • , Junwei Tang
    •  & Beicheng Sun

  • Article
    | Open Access

    Resident memory T cells (Trm) are memory T cells that remain in tissue. Here, the authors show that induction of Trm cells is required for control of tumour growth following mucosal vaccination in mice bearing head and neck cancer and that Trm cells in human lung cancer correlates with a better survival.

    • Mevyn Nizard
    • , Hélène Roussel
    •  & Eric Tartour

  • Article
    | Open Access

    The immunodominant epitope of dengue virus envelope protein (E) induces poorly neutralizing antibodies, which poses a problem for vaccine development. Here, the authors engineer covalently locked E dimers exposing an epitope that has been shown to induce potent and broadly neutralizing antibodies.

    • Alexander Rouvinski
    • , Wanwisa Dejnirattisai
    •  & Gavin R. Screaton

  • Article
    | Open Access

    Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.

    • Yuan Zhao
    • , Ann F. Gilliat
    •  & David Gems

  • Article
    | Open Access

    The cGAS-STING pathway is a DNA sensing mechanism that enables response to viral infection by inducing type 1 interferon expression. Here the authors show a mechanism by which the deubiquitinating enzyme USP13 prevents STING from enabling response to virus.

    • He Sun
    • , Qiang Zhang
    •  & Bo Zhong

  • Article
    | Open Access

    Antibodies against the platelet factor 4 (PF4) support bacterial host defence but in some cases may lead to heparin-induced thrombocytopenia (HIT). Nguyenet al.show that in autoimmune HIT a subset of antibodies binds strongly to PF4 causing its conformational change that leads to association of non-pathogenic PF4 antibodies and thrombotic platelet activation.

    • Thi-Huong Nguyen
    • , Nikolay Medvedev
    •  & Andreas Greinacher

  • Article
    | Open Access

    DNA degradation products are frequently found in the endosome, but how they regulate the activation of Toll-like receptors is not known. Here the authors show that single-stranded DNA as short as two nucleotides can enhance the ability of longer DNA oligonucleotides to activate Toll-like receptors.

    • Jelka Pohar
    • , Duško Lainšček
    •  & Mojca Benčina

  • Article
    | Open Access

    Tumour-specific T cells can be expandedin vitroand adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.

    • Taisuke Kondo
    • , Rimpei Morita
    •  & Akihiko Yoshimura

  • Article
    | Open Access

    TWEAK is a TNF family member that binds the NFκB signalling receptor Fn14. Here the authors show that TWEAK is central to skin inflammation in mouse models of atopic dermatitis and psoriasis and causes similar pathology when injected subcutaneously into mice.

    • Daniel Sidler
    • , Ping Wu
    •  & Michael Croft

  • Article
    | Open Access

    The molecular mechanism regulating macrophage interaction with endothelial cells during development is unclear. Here, the authors show that in zebrafish mutation of hypoxia-inducible factor-1α impairs macrophage mobilization from the aorta-gonad-mesonephros, causing defects in angiogenesis and vessel repair.

    • Claudia Gerri
    • , Rubén Marín-Juez
    •  & Didier Y R. Stainier

  • Article
    | Open Access

    Lambda interferons (IFNL) are involved in the immune response to viral infection. Here the authors show that zinc can interfere with IFNL signalling, and that in HCV patients the rs12979860 polymorphism regulates blood zinc levels and, subsequently, the hepatic immune response.

    • Scott A. Read
    • , Kate S. O’Connor
    •  & Golo Ahlenstiel

  • Article
    | Open Access

    Binding of T cell receptors (TCR) to peptide-loaded major histocompatibility complexes (p/MHC) leads to T-cell activation. Here the authors give structural insights into T-cell signalling and show that p/MHC binding induces conformational changes at the membrane-proximal site of the TCR.

    • Kannan Natarajan
    • , Andrew C. McShan
    •  & Nikolaos G. Sgourakis

  • Article
    | Open Access

    Regulatory T cells (Tregs) promote immune suppression in the tumour. Here, the authors show that Tregs suppress cytotoxic T lymphocyte (CTL) activity by impairing Ca2+ signalling and that adoptive transfer of CTLs engineered with an optogenetic control of Ca2+overcome the immune suppression at the tumour site.

    • Kyun-Do Kim
    • , Seyeon Bae
    •  & Minsoo Kim

  • Article
    | Open Access

    Broadly neutralizing antibodies (bnAbs) against influenza hemagglutinin (HA) have yielded insights for antiviral development. Here, the authors employ saturated mutagenesis of the paratope region of a bnAb combined with yeast display screening using H1 and H3 HAs, and find that a tradeoff exists between Ab affinity and breadth that influenced by disparate modes of receptor binding.

    • Nicholas C. Wu
    • , Geramie Grande
    •  & Ian A. Wilson

  • Article
    | Open Access

    IFN-γ signalling inhibits production of IL-9, the defining cytokine of the Th9 cell subset. Here the authors show that IFN-γ does this by driving IRF1 to compete with IRF4 forIl9promoter binding and skewing these cells towards a Th1 phenotype, an effect that reduces asthmatic inflammation in mice.

    • Lucia Campos Carrascosa
    • , Matthias Klein
    •  & Magdalena Huber

  • Article
    | Open Access

    Neutrophil adhesion is tightly regulated to enforce protective immunity, but it is unclear how mechanochemical processes such as catch bonds and slip bonds modulate neutrophilsin vivo. Here the authors show that a point mutation in the adhesion molecule L-selectin alters mechanochemical regulation to affect neutrophil functions in mice.

    • Zhenghui Liu
    • , Tadayuki Yago
    •  & Rodger P. McEver

  • Article
    | Open Access

    How NALP7 inflammasome formation is regulated is unclear. Here the authors show that STAMBP prevents lysosomal degradation of NALP7 and present BC-1471 as a potential therapeutic STAMBP inhibitor, showing it can reduce TLR-induced IL-1β production.

    • Joseph S. Bednash
    • , Nathaniel Weathington
    •  & Rama K. Mallampalli

  • Article
    | Open Access

    Long-term consumption of a calorie-rich diet persistently activates brain microglia. Here, the authors show that microglial activity in mouse brains oscillates daily in conjunction with feeding, and that TNFα, secreted by activated microglia, induces mitochondrial stress in satiety-promoting POMC neurons.

    • Chun-Xia Yi
    • , Marc Walter
    •  & Matthias H. Tschöp

  • Article
    | Open Access

    Tumour repopulating cells (TRC) are stem-like cells that can escape immune-mediated killing. Here, the authors show IFN-γ results in either dormancy or apoptosis of TRC depending on the activation of the IDO1 metabolic pathway, and that combining IFN-γ with IDO1 inhibitors results in enhanced tumour regression.

    • Yuying Liu
    • , Xiaoyu Liang
    •  & Bo Huang

  • Article
    | Open Access

    Interleukin-6 (IL-6) is increased in obesity and activates T cells to promote inflammation. Here, Xuet al. use mice that lack IL-6 receptors on T cells to uncover the temporal and tissue-specific effects of classic and trans IL-6 signalling on inflammation and insulin resistance on a high-fat diet.

    • Elaine Xu
    • , Mafalda M. A. Pereira
    •  & Jens C. Brüning

  • Article
    | Open Access

    Virus-specific CD8+T cells lose effector function over the course of chronic infection, a process called ‘exhaustion’, but the fate of these cells after treatment-induced antigen elimination is unknown. Here the authors show that exhausted cells persist in patients even after direct-acting antiviral therapy removes antigen exposure, and that these cells are responsive on re-exposure to antigen.

    • Dominik Wieland
    • , Janine Kemming
    •  & Robert Thimme

  • Article
    | Open Access

    Laboratory mice are the cornerstone of immunology but how well they represent wild mice is not clear. Here the authors compare and contrast various immune parameters between wild-caught mice and laboratory (C57BL/6) mice and identify a previously unknown myeloid cell population specific to wild mice.

    • Stephen Abolins
    • , Elizabeth C. King
    •  & Eleanor M. Riley

  • Article
    | Open Access

    The coevolution of viruses and host cells can be mapped with interactomics. Here the authors identify coupling of human and viral promoters, and show that HIV-reactivation from dormancy is coincident with migration of HIV-infected cells owing to coupling of human CXCR4 and HIV LTR promoters.

    • Kathrin Bohn-Wippert
    • , Erin N. Tevonian
    •  & Roy D. Dar

  • Article
    | Open Access

    In vitro models to study the role of host genetics in the response to chlamydial infection are limited. Here, Yeung et al. show that macrophages derived from human induced pluripotent stem cells (which can be genetically manipulated) support chlamydial infection and can be used for this purpose.

    • Amy T. Y. Yeung
    • , Christine Hale
    •  & Robert E. W. Hancock

  • Article
    | Open Access

    Neurons can convert pathogenic T cells to anti-inflammatory FoxA1+ regulatory T cells (Tregs), which can ameliorate EAE, but the molecular mechanism is only partially understood. Liu et al. show that autocrine interferon β signalling induces PDL1 expression in neurons, which is essential for neurons to reprogramme pathogenic T cells to FoxA1+ Tregs.

    • Yawei Liu
    • , Andrea Marin
    •  & Shohreh Issazadeh-Navikas

  • Article
    | Open Access

    T follicular helper and regulatory cells are generated in the germinal centre; however, whether antigen specificity defines their differential functions is unclear. Here the authors show that T cells with distinct antigen specificity spectra are recruited to the germinal centre to establish these two populations.

    • Ana Raquel Maceiras
    • , Silvia Cristina Paiva Almeida
    •  & Luis Graca

  • Article
    | Open Access

    B-cell encounter with antigen is thought to result in anergy, cell death, or a productive B-cell response. Here the authors show that transient antigen acquisition can enable B-cell recruitment into productive responses or a return to a naive-like state, depending on availability of T-cell help.

    • Jackson S. Turner
    • , Matangi Marthi
    •  & Irina Grigorova

  • Article
    | Open Access

    Professional antigen presenting cells (APC) are the major activator of T cells that then hone to sites of inflammation. Using islet cell grafts, here the authors show that parenchymal cells can present antigen to activate CD8+T cells at inflammatory sites, coining this a ‘mezzanine response’ distinct from primary and secondary responses associated with professional APCs.

    • Robyn M. Sutherland
    • , Sarah L. Londrigan
    •  & Andrew M. Lew

  • Article
    | Open Access

    Patients who survive sepsis are at increased risk of infection owing to long-term immunosuppression that is associated with an increase in Treg cell numbers. Here the authors show expansion of the Treg cell population in sepsis mice is driven by IL-33-induced ILC2 activation of IL-10 production by macrophages.

    • Daniele C. Nascimento
    • , Paulo H. Melo
    •  & Jose C. Alves-Filho

  • Article
    | Open Access

    The cell type that hosts parvovirus B19 (B19V) DNA lifelong is currently unknown. Here, the authors identify tonsillar B cells as a reservoir, detect an extinct B19V type in older adults, supporting a long-term association, and show that B19V uptake into B cells is antibody dependent.

    • Lari Pyöriä
    • , Mari Toppinen
    •  & Maria F. Perdomo

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