Featured
-
-
Article
| Open AccessA toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages
Turning tumour promoting macrophages into an anti-tumour phenotype is an attractive therapeutic strategy. Here, the authors develop a polysaccharide-based structure that mimicks pathogen-associated molecular patterns and, by activating the toll-like receptors on macrophage surface, promotes a safe anti-tumour immune response in mouse models.
- Yanxian Feng
- , Ruoyu Mu
- & Chunming Wang
-
Article
| Open AccessCTL-mediated immunotherapy can suppress SHIV rebound in ART-free macaques
Viral rebound following discontinuation of antiretroviral therapy (ART) is a major obstacle for HIV cure. Here, the authors show that adoptive cellular therapy using autologous Env-specific T cells augmented by therapeutic vaccination can control viral rebound after ART interruption in a SHIV macaque model.
- Jin Fan
- , Hua Liang
- & Yiming Shao
-
Article
| Open AccessDiverse MR1-restricted T cells in mice and humans
Mucosal-associated invariant T (MAIT) cells express invariant TRAV1/TRAJ33 TCR-α gene segments and detect antigens presented by MR1. Here the authors show that atypical, MR1-restricted MAIT populations that include both Trav1+ and Trav1- cells are found in both Traj33-deficient mice and human peripheral blood.
- Hui-Fern Koay
- , Nicholas A. Gherardin
- & Dale I. Godfrey
-
Article
| Open AccessDevelopment of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression
Cyclic GMP-AMP synthase (cGAS) is involved in the modulation of inflammatory responses. Here, the authors present small-molecule inhibitors of human cGAS, characterize their interaction with the protein, and show that the compounds are active in interferon-producing cells including primary human macrophages.
- Lodoe Lama
- , Carolina Adura
- & Thomas Tuschl
-
Article
| Open AccessDevelopment of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
The development of tissue-engineered vascular grafts heavily relies on the availability of large animal models that allow long-term assessment of graft patency. Here Itoh et al. propose a novel model of immunodeficient pigs that allows long-term accommodation of human cell-derived three-dimensional bioprinted vascular tubes.
- Manabu Itoh
- , Yosuke Mukae
- & Eiji Kobayashi
-
Article
| Open AccessZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Complement activation contributes to vascular inflammation in the contexts of allograft rejection and connective tissue disease. Here Fang et al. identify ZFYVE21 as a novel effector of Rab5 and find it regulates pro-inflammatory NF-κB signaling in endothelial cells in response to complement activation.
- Caodi Fang
- , Thomas D. Manes
- & Dan Jane-wit
-
Article
| Open AccessOptimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity
Agonistic 4-1BB antibodies developed for cancer immunotherapy have suffered from either hepatotoxicity or insufficient anti-cancer activity. Here the authors determine the contribution of FcγR binding and agonistic strength to these outcomes, and engineer a 4-1BB antibody with potent anti-tumor effect and no liver toxicity in mice.
- Xinyue Qi
- , Fanlin Li
- & Xuanming Yang
-
Article
| Open AccessLive-cell imaging reveals the relative contributions of antigen-presenting cell subsets to thymic central tolerance
Both thymic epithelial cells and dendritic cells present self antigens in the thymus to mediate thymic selection and T cell tolerance. Here the authors quantify, using two-photon live imaging of mouse thymic slices, the relative contribution of these two cell types, as well as the effects of antigen cross-presentation by dendritic cells, during tolerance induction.
- J. N. Lancaster
- , H. M. Thyagarajan
- & L. I. R. Ehrlich
-
Article
| Open AccessSkin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8+ effector recruitment to mucosal tissues
Mucosal immunisation is important for initiating mucosal CD8+ Tcell responses but mucosal recruitment of protective CD8+ T cells can also be induced by skin immunisation. Here the authors examine the underlying mechanism and report a novel role for ILC1 recruiting CD8+ T cells to the mucosa after skin immunisation.
- Marija Zaric
- , Pablo D. Becker
- & Linda S. Klavinskis
-
Article
| Open AccessFunctional rare and low frequency variants in BLK and BANK1 contribute to human lupus
Function-altering variants of immune-related genes cause rare autoimmune syndromes, whereas their contribution to common autoimmune diseases remains uncharacterized. Here the authors show that rare variants of lupus-associated genes are present in the majority of lupus patients and healthy controls, but only the variants found in lupus patients alter gene function.
- Simon H. Jiang
- , Vicki Athanasopoulos
- & Carola G. Vinuesa
-
Article
| Open AccessAirway response to respiratory syncytial virus has incidental antibacterial effects
Respiratory syncytial virus (RSV) can trigger secondary airway bacterial infections. Here, by proteomics and metagenomics analyses of samples from Kenyan children, the authors report that RSV associates with Streptococcus burden and a local upper airway response with direct antibacterial properties.
- Charles J. Sande
- , James M. Njunge
- & Andrew J. Pollard
-
Article
| Open AccessKappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage
Development of broadly neutralizing antibodies (bnAb) against HIV-1 in infected adults is a multi-step process unachievable by current vaccine approaches. Here the authors reconstruct the ontogeny of an infant bnAb, which develops in fewer steps, and identify its unique features that may shorten the path to HIV vaccines.
- Cassandra A. Simonich
- , Laura Doepker
- & Julie Overbaugh
-
Article
| Open AccessInnate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo
Tissue signals that prime autoreactive T cells at the onset of autoimmunity remain enigmatic. Here the authors show NK and ILC1 cells are increased in vitiligo patients, and induce melanocyte apoptosis via CXCR3B, which in turn leads to increased priming of T cell responses in cell culture.
- Meri K. Tulic
- , Elisa Cavazza
- & Thierry Passeron
-
Article
| Open AccessConcentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy
RTS,S/AS01E has been tested in a phase 3 malaria vaccine trial and has shown partial efficacy in children and infants. Here, the authors analyze IgG concentration and avidity to CSP in ~1000 participants and show that IgG avidity to the C-terminus of CSP is significantly associated with vaccine-mediated protection.
- Carlota Dobaño
- , Hèctor Sanz
- & Claudia Daubenberger
-
Article
| Open AccessJoint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Streptococcus pneumoniae is a causative agent of meningitis and bacteremia. In a combined pathogen and host GWAS, Lees et al. find that host genetic variation is associated with both susceptibility and severity of pneumococcal meningitis, and specific bacterial genetic variation associated with susceptibility.
- John A. Lees
- , Bart Ferwerda
- & Diederik van de Beek
-
Article
| Open AccessInterferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) shows a striking bias towards higher prevalence in females. Here, the authors perform fine-mapping of an SLE-associated locus at Xp21.2 and characterise a candidate gene, CXorf21, as IFN-responsive in immune cells that shows sexually dimorphic expression.
- Christopher A. Odhams
- , Amy L. Roberts
- & Timothy J. Vyse
-
Article
| Open AccessmiR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate
The inability of T cells to properly mount anti-tumour immunity underlies failed cancer immune surveillance or therapy. Here the authors show that a microRNA, miR-155, suppresses Ship1 phosphatase expression to modulate epigenetic reprogramming of CD8 T cell differentiation via the Phf19/PRC2 axis, thereby implicating a novel aspect of cancer immunity regulation.
- Yun Ji
- , Jessica Fioravanti
- & Luca Gattinoni
-
Article
| Open AccessIL-1β, IL-23, and TGF-β drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation
Innate lymphoid cells (ILCs) play critical immunological roles including immune surveillance at mucosal sites. Here the authors show that during nasal inflammation pathogen-induced cytokine production guides the differentiation of ILCs.
- Korneliusz Golebski
- , Xavier R. Ros
- & Suzanne M. Bal
-
Article
| Open AccessSuppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines
Immune response against tissue-specific antigens is a hallmark of autoimmunity. Here the authors show that a single autoantigen-based nanomedicine can ameliorate pathology in a broad range of liver autoimmunity models without impairing host defenses, suggesting organ-wide tolerization.
- Channakeshava Sokke Umeshappa
- , Santiswarup Singha
- & Pere Santamaria
-
Article
| Open AccessBacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis
The capsular polysaccharide A (PSA) of Bacteroides fragilis is known to have immunomodulatory capability during sterile inflammatory disorders. Here Ramakrishna and colleagues show that PSA administration in a murine model of herpes simplex encephalitis induces IL-10 producing B and T cell populations that confer protection against lethal challenge and brain pathology.
- Chandran Ramakrishna
- , Maciej Kujawski
- & Edouard M. Cantin
-
Article
| Open AccessCD200R deletion promotes a neutrophil niche for Francisella tularensis and increases infectious burden and mortality
The authors show that the CD200 receptor (CD200R) promotes effective clearance of pulmonary Francisella tularensis infection in knock out mice. This result is unexpected as CD200R is known to dampen pulmonary immune responses, and these data suggest that the beneficial effect against F. tularensis is due to depletion of a neutrophil niche for the bacterium.
- J. Casulli
- , M. E. Fife
- & M. A Travis
-
Review Article
| Open AccessCompetition for nutrients and its role in controlling immune responses
Immune cells adapt distinct metabolic strategies to accommodate specific functions associated with cell types or differentiation stages. Here in this review the authors discuss the nutrients, sensors, and mediators of such a metabolic adaption in nutrient-limiting immune microenvironments such as tumors or infections.
- Nidhi Kedia-Mehta
- & David K. Finlay
-
Article
| Open AccessSox17 is required for endothelial regeneration following inflammation-induced vascular injury
Endothelial cell regeneration is essential for blood vessels to recover from inflammation-induced injury. Here Liu et al. show that the transcription factor Sox17 is required for endothelial regeneration following endotoxemia, and that delivery of a transgene expressing Sox17 to lung endothelial cells enhances recovery after injury.
- Menglin Liu
- , Lianghui Zhang
- & Asrar B. Malik
-
Article
| Open AccessSynthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response
Supraphysiological T cell activation by chimeric antigen receptor (CAR) contributes to T cell exhaustion and adverse events in CAR T cell therapies. Here the authors engineer a synthetic antigen receptor that integrates into the endogenous TCR complex, preserving natural regulatory circuits and achieving improved performance in mouse tumor models.
- Patrick A. Baeuerle
- , Jian Ding
- & Robert Hofmeister
-
Article
| Open AccessCaspase-1 initiates apoptosis in the absence of gasdermin D
In inflammasomes, caspase-1 activation leads to pyroptosis mediated by gasdermin D, but cells lacking gasdermin-D still initiate caspase-dependent cell death. Here, Tsuchiya et al. show that these cells undergo Bid- and caspase-3-dependent apoptosis.
- Kohsuke Tsuchiya
- , Shinsuke Nakajima
- & Takashi Suda
-
Article
| Open AccessDNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis
Monozygotic (MZ) twins are ideal to study the influence of non-genetic factors on complex phenotypes. Here, Souren et al. perform an EWAS in peripheral blood mononuclear cells from 45 MZ twins discordant for multiple sclerosis and identify disease and treatment-associated epigenetic markers.
- Nicole Y. Souren
- , Lisa A. Gerdes
- & Jörn Walter
-
Article
| Open AccessSingle-molecule kinetics of pore assembly by the membrane attack complex
The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. Here, the authors use atomic force microscopy to show that MAC proteins oligomerize within the membrane, allowing them to identify the kinetic bottleneck of MAC formation.
- Edward S. Parsons
- , George J. Stanley
- & Bart W. Hoogenboom
-
Article
| Open AccessAkt and STAT5 mediate naïve human CD4+ T-cell early metabolic response to TCR stimulation
T-cell subsets differ in metabolic requirements for particular tasks. Here the authors characterize metabolic fluxes in naïve human CD4+ cells upon activation, and identify a role of Stat5 in glutaminolysis linked to IL-2 production.
- Nicholas Jones
- , Emma E. Vincent
- & Catherine A. Thornton
-
Article
| Open AccessLoss of TET2 and TET3 in regulatory T cells unleashes effector function
Loss of TET proteins in immune cell populations is known to result in immunopathology. Here the authors show that deficiency of Tet2 and Tet3 proteins, specifically in the CD4+ FoxP3+ Treg lineage, results in a dominant pathology in which ex-Treg cells and bystander T cells gain aberrant effector function.
- Xiaojing Yue
- , Chan-Wang J. Lio
- & Anjana Rao
-
Article
| Open AccessCXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis
CXCL4 is an inflammatory chemokine signaling through CXCR3 receptor. Here the authors show a CXCR3-independent function of CXCL4: it forms liquid crystals with DNA, potentiating mammalian and bacterial DNA recognition by TLR9, thereby amplifying interferon-a production in systemic sclerosis.
- Roberto Lande
- , Ernest Y. Lee
- & Loredana Frasca
-
Article
| Open AccessLipopolysaccharide inhalation recruits monocytes and dendritic cell subsets to the alveolar airspace
The diversity of human mononuclear phagocyte subsets remains to be characterized in many tissue-specific and functional contexts, including pulmonary inflammation. Here the authors characterize dendritic cell and monocyte subset recruitment to the bronchoalveolar space in a human LPS inhalation model.
- Laura Jardine
- , Sarah Wiscombe
- & A. John Simpson
-
Article
| Open AccessFcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human
The inhibitory receptor, FcγRIIb, is reported to limit autoimmune B cell response. Here the authors show that FcγRIIb has a dual role in both human and mouse, with reduced FcγRIIb expression or function associated with enhanced pre-immune B cell tolerance, yet defective control of mature autoreactive B cells in the germinal center.
- Marion Espéli
- , Rachael Bashford-Rogers
- & Kenneth G. C. Smith
-
Article
| Open AccessA Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy
Ubiquitin (Ub)-mediated xenophagy is important in defense against Mycobacterium tuberculosis (Mtb). Here, Chai et al. describe autophagy triggering by Ub binding to the Mtb surface protein Rv1468c, and show that its deletion leads to increased bacterial loads and hyperinflammatory responses in mice.
- Qiyao Chai
- , Xudong Wang
- & Cui Hua Liu
-
Article
| Open AccessA defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates
Proof of protection against blood-stage P. falciparum malaria by a single immunological mechanism has been elusive. Here, using engineered anti-PfRH5 chimeric monoclonal antibodies in non-human primates, the authors show that high levels of merozoite-neutralizing antibodies can achieve protection.
- Alexander D. Douglas
- , G. Christian Baldeviano
- & Simon J. Draper
-
Article
| Open AccessDynamic gene regulation by nuclear colony-stimulating factor 1 receptor in human monocytes and macrophages
Receptor tyrosine kinases localize to the cell surface and have been suggested to also have nuclear function. Here the authors provide evidence that Colony Stimulating Factor-1 Receptor (CSF-1R) migrates to the nucleus upon CSF-1 stimulation in monocytes and that upon differentiation into macrophages, CSF-1R localizes to TSS, co-localizes with H3K4me3, and interacts with ELK and YY1.
- Laura Bencheikh
- , M’Boyba Khadija Diop
- & Nathalie Droin
-
Article
| Open AccessDifferential human antibody repertoires following Zika infection and the implications for serodiagnostics and disease outcome
In the current study, the authors profile the IgG and IgM antibody repertoires that develop over 7 days following acute Zika virus infection. Using urine and serum samples from infected human patients the authors identify new biomarkers for serodiagnosis of Zika virus.
- Supriya Ravichandran
- , Megan Hahn
- & Surender Khurana
-
Article
| Open AccessSpatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma
Granulomas are a hallmark and focus of infective and immunological processes during infection with Mycobacterium tuberculosis. Here, Carow and colleagues show distinct spatial and temporal arrangement of immunological transcripts in tuberculosis granulomas.
- Berit Carow
- , Thomas Hauling
- & Martin E. Rottenberg
-
Article
| Open AccessMettl3-mediated mRNA m6A methylation promotes dendritic cell activation
Here the authors examine how m6A modification is involved in innate immunity. They show that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function, and in promoting DC-based T cells responses.
- Huamin Wang
- , Xiang Hu
- & Xuetao Cao
-
Article
| Open AccessCharacterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing
Adaptive immunity from both B and T cells critically controls the rejection or survival of transplanted organs. Here the authors show, by analyzing human B cell receptor repertoire in longitudinal studies of patients receiving kidney transplants, that repertoire diversity is positively associated with the incidence of kidney rejection.
- Silvia Pineda
- , Tara K. Sigdel
- & Minnie M. Sarwal
-
Article
| Open AccessPhysical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis
Maintaining the intestinal barrier function requires a balance of multiple signalling pathways. Here the authors show that A20, an anti-inflammatory and anti-apoptotic protein, and Atg1611, an autophagy regulator, cross-regulate their respective protein levels and function to serve compensatory and redundant roles in fine-tuning gut barrier homeostasis.
- Karolina Slowicka
- , Inmaculada Serramito-Gómez
- & Geert van Loo
-
Article
| Open AccessAdenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome
Antiphospholipid syndrome is characterised by increased neutrophil extracellular trap formation (NETosis) and, consequently, increased thrombotic events. Here Ali et al. show that treatment with adenosine receptor agonists suppresses NETosis and venous thrombosis in mouse models of antiphospholipid syndrome.
- Ramadan A. Ali
- , Alex A. Gandhi
- & Jason S. Knight
-
Article
| Open AccessMultifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes
Possible immunogenicity of the Cas9 protein raises concerns about therapeutic applications. Here the authors identify pre-existing CD8+T-cell immunity in healthy individuals and in response modify Cas9 to remove the immunodominant epitopes.
- Shayesteh R. Ferdosi
- , Radwa Ewaisha
- & Karen S. Anderson
-
Article
| Open AccessA small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development
Loss of cartilage tissue is a hallmark of osteoarthritis. Here the authors show that BNTA, a small molecule identified in a chemical screen, promotes ECM generation in human osteoarthritic chondrocytes and cartilage explants, and suppresses pathology in a rat model of osteoarthritis.
- Yuanyuan Shi
- , Xiaoqing Hu
- & Yingfang Ao
-
Article
| Open AccessMajor vault protein suppresses obesity and atherosclerosis through inhibiting IKK–NF-κB signaling mediated inflammation
Metabolic diseases are associated with chronic, low-grade inflammation. Here the authors show that major vault protein (MVP) suppresses NF-κB signalling in macrophages via an IRAK1–TRAF6 axis and that loss of MVP in myeloid cells exacerbates the inflammatory response in mice fed a high fat diet.
- Jingjing Ben
- , Bin Jiang
- & Qi Chen
-
Article
| Open AccessThe role of platelets in mediating a response to human influenza infection
Influenza viremia is rare in human blood and not well studied. Here, the authors show that influenza can be found in human platelets and that platelet engulfment of influenza A results in TLR7-dependent C3 release, which in turn promotes neutrophil-DNA release and formation of platelet-DNA aggregates.
- Milka Koupenova
- , Heather A. Corkrey
- & Jane E. Freedman
-
Article
| Open AccessSerine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation
RIPK1 kinase activity is known to transduce a death signal, but the molecular mechanisms that normally prevent RIPK1 activation are unclear. Here, the authors report that IKK-mediated phosphorylation on RIPK1 Ser25 directly represses its enzymatic activity and thus RIPK1-dependent cell death.
- Yves Dondelinger
- , Tom Delanghe
- & Mathieu J. M. Bertrand
-
Article
| Open AccessOrigin and differentiation trajectories of fibroblastic reticular cells in the splenic white pulp
The white pulp of spleen is an important immune structure dynamically modulated during development and immune responses. Here the authors define, using multi-color lineage tracing and single-cell transcriptome analysis, the subset distribution and differentiation trajectory of fibroblastic reticular cells to serve structural insights for splenic white pulps.
- Hung-Wei Cheng
- , Lucas Onder
- & Burkhard Ludewig
-
Article
| Open AccessImpaired cellular energy metabolism in cord blood macrophages contributes to abortive response toward inflammatory threats
Neonatal immune responses are known to differ to those of an adult immune response. Here Dreschers and colleagues, compare macrophage populations derived from cord blood or adult peripheral blood and show a metabolic impairment of glycolysis in macrophages derived from cord blood which may impair response to infective scenarios such as sepsis.
- Stephan Dreschers
- , Kim Ohl
- & Klaus Tenbrock
-
Article
| Open AccessGasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation
Gasdermins mediate lytic cell death by forming pores in the plasma membrane. Here the authors show that gasdermins also permeabilize mitochondrial membrane, thereby facilitating intrinsic apoptosis pathway, downstream of apoptotic (Gasdermin E) and inflammatory (Gasdermin D) caspase activation.
- Corey Rogers
- , Dan A. Erkes
- & Emad S. Alnemri
Browse broader subjects
Browse narrower subjects
- Adaptive immunity
- Antigen processing and presentation
- Antimicrobial responses
- Applied immunology
- Autoimmunity
- Bone marrow transplantation
- Cell death and immune response
- Chemokines
- Coagulation system
- Complement cascade
- Cytokines
- Gene regulation in immune cells
- Haematopoiesis
- Imaging the immune system
- Immune cell death
- Immune evasion
- Immunogenetics
- Immunological disorders
- Immunotherapy
- Infection
- Infectious diseases
- Inflammation
- Innate immune cells
- Innate immunity
- Lymphatic system
- Lymphocytes
- Lymphoid tissues
- Mucosal immunology
- Neuroimmunology
- Osteoimmunology
- Plant immunology
- Signal transduction
- Translational immunology
- Transplant immunology
- Tumour immunology
- Vaccines