Research Highlights

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    Like bacteria, T cells are reported to communicate with each other and adapt their behaviour according to cell density. This quorum regulation supports T cell population expansion and contraction in response to infection.

    • Lucy Bird
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    Febrile temperature increases the differentiation of T helper 17 (TH17) cells with a more pro-inflammatory, pathogenic phenotype, which could have implications for the pathogenesis of autoimmunity.

    • Kirsty Minton
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    Plant root cells upregulate pattern recognition receptors for bacteria in response to damage to neighbouring cells.

    • Yvonne Bordon
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    McGinley et al. describe a new role for IL-17A in the induction phase of experimental autoimmune encephalomyelitis by indirectly recruiting IL-1β-producing myeloid cells.

    • Kirsty Minton
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    Researchers identify a new population of cytotoxic T cells that recognize the non-polymorphic MHC class I-related molecule MR1 on multiple different cancer cells, raising the prospect of its use as T cell-based therapy for multiple cancers.

    • Lucy Bird
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    The ‘shock-and-kill’ strategy aims to eradicate HIV by luring the virus out of hiding, followed by killing of the virus and any infected cells. Two reports now demonstrate robust approaches to achieve the first step of such a strategy.

    • Alexandra Flemming
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    VEGF-C enhances T cell priming against brain tumours and improves the efficacy of immune checkpoint blockade in a model of glioblastoma.

    • Yvonne Bordon
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    The host aryl hydrocarbon receptor can detect various quorum-sensing molecules produced by Pseudomonas aeruginosa, which may allow host immune cells to tune their response according to the bacterial density.

    • Kirsty Minton
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    T cells expressing programmed cell death 1 (PD1) have been considered the main targets of immune checkpoint blockade therapy. But a new study shows that targeting PD1 on myeloid cells reprogrammes tumour-induced myelopoiesis to favour maturation of effector myeloid cells that promote antitumour immunity.

    • Lucy Bird
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    Somatic mutations conferring resistance to IL-17A-mediated apoptosis accumulate in the inflamed epithelium of patients with ulcerative colitis.

    • Yvonne Bordon
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    The design of vaccines that induce broadly neutralizing antibodies (bnAbs) to HIV is extremely challenging. Two reports now demonstrate strategies for the design of immunogens that can induce the production of bnAb precursors and guide these towards the acquisition of improbable mutations.

    • Alexandra Flemming
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    Overexpression of JUN by CAR T cells renders them resistant to exhaustion and improves tumour control in mouse models, including of solid tumours and of tumours with low levels of antigen expression.

    • Kirsty Minton
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    Endogenous oxidized phospholipids can induce a hypermetabolic state in macrophages, involving both oxidative phosphorylation and aerobic glycolysis, that boosts the inflammatory response to lipopolysaccharide.

    • Kirsty Minton
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    A trispecific antibody that provides T cell co-stimulation shows promise in preclinical models of myeloma.

    • Alexandra Flemming
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    The benefits of exercise reach the bone marrow, altering haematopoietic cell niches and regulating inflammatory cell output.

    • Lucy Bird
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    Chen Dong and colleagues describe a positive-feedback loop between TOX2 and BCL-6 that helps to drive the development of T follicular helper cells in germinal centres.

    • Kirsty Minton
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    Collaboration is key when it comes to mounting an effective T cell response against cancer. A new study shows that CD4+ T cell activation in a tumour is required to support effective priming and cytotoxic activity of tumour-infiltrating CD8+ T cells.

    • Lucy Bird
  • Research Highlight |

    Commensal viruses in the intestine support the proliferation and survival of intraepithelial lymphocytes through RIG-I-dependent IL-15 production and therefore contribute to healthy gut homeostasis.

    • Kirsty Minton
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    IL-17-producing γδ T cells in the meningeal spaces support short-term spatial memory formation.

    • Yvonne Bordon
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    A new study has identified genetic variants of the anti-inflammatory signalling molecule A20 that can be traced back to archaic humans and affect microbial resistance versus tolerance.

    • Lucy Bird
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    Two new studies define the liver-derived signals that promote Kupffer cell development from a common monocyte precursor.

    • Yvonne Bordon
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    This study investigates the roles of mutational burden and clonal heterogeneity in immune responses to melanoma and finds that low tumour heterogeneity is a predictor of favourable responses to immunotherapy.

    • Alexandra Flemming
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    Two papers by Gregory Barton and colleagues identify distinct UNC93B1-dependent mechanisms for regulation of the endosomal nucleic acid-sensing TLRs, TLR7 and TLR9.

    • Kirsty Minton
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    Chimeric antigen receptor (CAR) T cells directed at fibroblast activation protein show efficacy in mouse models of hypertensive cardiac injury and fibrosis.

    • Sarah Crunkhorn
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    Antibiotics can impair the development of immunity against seasonal influenza virus in individuals with low levels of pre-existing immune memory.

    • Yvonne Bordon
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    Commensal bacteria at mucosal surfaces can remotely control the thymic maturation of mucosal-associated invariant T cells through the production of microbial factors that enter the circulation and are taken up by thymic cells.

    • Kirsty Minton
  • Research Highlight |

    A new study shows that monocytes, recruited to the lungs during an infection, sense alterations in physical forces and pressure and initiate a pro-inflammatory response. This environmental sensory axis is mediated by the mechanically activated calcium channel PIEZO1.

    • Lucy Bird
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    Fasting can modulate immune responses in the context of infection, inflammatory disease and cancer.

    • Yvonne Bordon
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    The angiogenic growth factor placental growth factor is produced by TH17 cells and induces TH17 cell differentiation, which suggests a positive feedback loop between angiogenesis and autoimmunity in chronically inflamed tissues.

    • Kirsty Minton
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    Class-switch recombination was thought to take place in B cells that enter germinal centres, but this study shows that it actually occurs earlier than previously thought.

    • Alexandra Flemming
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    Targeting metabolism via mTOR restores suppressor functions in FOXP3-deficient regulatory T cells.

    • Yvonne Bordon
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    Chimeric antigen receptor (CAR) T cells that secrete bispecific T cell engagers (BiTEs) show promise for the treatment of glioblastoma in mouse models.

    • Alexandra Flemming
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    Metabolites associated with the maternal or neonatal microbiota can shape regulatory T cell development in early life, thereby affecting the susceptibility of infants to allergy.

    • Yvonne Bordon
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    Stimulation of cutaneous TRPV1+ neurons is sufficient to induce a type 17 inflammatory response that spreads to surrounding skin areas to provide ‘anticipatory’ host defence against fungal infection.

    • Kirsty Minton
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    Researchers have identified a subset of T helper cells that is found predominantly in individuals with multiple sclerosis. The subset is defined by expression of GM-CSF and CXCR4 and may be important in disease pathology.

    • Lucy Bird
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    Leukaemia stem cells seem to evade immune surveillance by repressing the expression of stress-induced activating natural killer (NK) cell ligands. Overriding this repression with inhibitors renders them amenable to control by NK cells and prevents leukaemogenesis.

    • Lucy Bird
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    Cytosolic protein oligomers formed by certain innate immune receptors and their adaptor proteins trigger the integrated stress response pathway, which regulates the stability of these signalosomes as well as downstream inflammatory responses.

    • Kirsty Minton
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    A new study shows that neutrophils collaborate with tumour-associated macrophages and unconventional innate-like T cells to mount type 1 antitumour immunity.

    • Lucy Bird
  • Research Highlight |

    This study demonstrates that TREM1, an amplifier of inflammation, is induced on peripheral myeloid cells in response to stroke and uncovers an intriguing connection between the brain, the gut and the immune system.

    • Alexandra Flemming
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    Six studies describe a role for TOX in promoting an ‘exhausted’ CD8+ T cell phenotype in settings of chronic antigenic stimulation, such as persistent viral infections and cancer.

    • Yvonne Bordon
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    Levels of CCR5 expression by CD4+ T cells, which influence the outcome of HIV-1 infection, are modulated by polymorphism of a non-coding RNA that affects mRNA stability.

    • Kirsty Minton
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    Antibodies that dissolve Charcot–Leyden crystals may have therapeutic potential in asthma and other eosinophil-associated inflammatory diseases.

    • Yvonne Bordon
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    Trifunctional antibodies, binding to the natural killer cell receptors NKp46 and CD16, as well as a tumour antigen, show promising activity in preclinical experiments.

    • Alexandra Flemming
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    A new study identifies an unexpected role for type I interferon-responsive CD8+ T cells in cachexia associated with viral infection.

    • Lucy Bird