Featured
-
-
Article
| Open AccessThe chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis
The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.
- Kathryn Weinand
- , Saori Sakaue
- & Soumya Raychaudhuri
-
Article
| Open AccessTwo noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
- Runchu Zhao
- , Lili Wu
- & Qihui Wang
-
Article
| Open AccessUniversal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.
- Johannes P. M. Langedijk
- , Freek Cox
- & Mark J. G. Bakkers
-
Article
| Open AccessStatin prevents cancer development in chronic inflammation by blocking interleukin 33 expression
Interleukin-33 (IL-33) is a master initiator of cancer-prone chronic inflammation. Here, the authors show that TLR3/4-TBK1-IRF3 pathway activation induces IL-33, and the cholesterol-lowering drug, statin, blocks this pathway to suppress chronic inflammation and its cancer sequela.
- Jong Ho Park
- , Mahsa Mortaja
- & Shadmehr Demehri
-
Article
| Open AccessGene expression signatures in blood from a West African sepsis cohort define host response phenotypes
Sepsis is a global challenge and a significant burden in Sub-Saharan Africa. Here, Chenoweth et al profile host gene expression signatures from a cohort in Ghana to define molecular phenotypes and identify potential targets to improve patient outcomes.
- Josh G. Chenoweth
- , Carlo Colantuoni
- & Danielle V. Clark
-
Article
| Open AccessSmall molecule induced STING degradation facilitated by the HECT ligase HERC4
In this paper, Mutlu et al. identifies a STING degrader, AK59, which inhibits downstream cGAS/STING activity through STING degradation employing a HECT-domain E3 ligase HERC4 and proteasomal ubiquitination pathway.
- Merve Mutlu
- , Isabel Schmidt
- & Danilo Guerini
-
Article
| Open AccessLiver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis
Novel short-acting IL-22 bispecific biologics offer new hope for treating metabolic dysfunction-associated steatohepatitis (MASH), a global health concern with few treatment options. Here, the authors show these drugs significantly improve blood sugar control, liver fat, inflammation, and scarring.
- Haressh Sajiir
- , Sahar Keshvari
- & Sumaira Z. Hasnain
-
Article
| Open AccessPancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis
IL-22RA1 is highly expressed on pancreatic islets and absent on immune cells. Here, the authors investigate its role by generating animals that lack IL-22RA1 on beta cells and reveal IL22RA1 signalling is critical for insulin biosynthesis and beta-cell health, evidenced by its regulation of MHC II expression and its suppressive effect on inflammation and cellular stress.
- Haressh Sajiir
- , Kuan Yau Wong
- & Sumaira Z. Hasnain
-
Article
| Open AccessMemory CD8 T cells are vulnerable to chronic IFN-γ signals but not to CD4 T cell deficiency in MHCII-deficient mice
Memory CD8+ T cells persist poorly in MHCII-deficient mice. Here the authors show that this CD8+ T cell attrition is not caused by a lack of CD4+ T cell help, as previously proposed, but by chronic IFN-γ signals derived from endogenous colonic CD8+ T cells.
- Ruka Setoguchi
- , Tomoya Sengiku
- & Shohei Hori
-
Article
| Open AccessLong-read sequencing for 29 immune cell subsets reveals disease-linked isoforms
This paper unveils the complexity of human immune cell splicing, highlighting cell-specific isoforms and establishing connections between alternative splicing and complex traits. These findings have implications for understanding diseases and the evolution of the genome.
- Jun Inamo
- , Akari Suzuki
- & Yuta Kochi
-
Article
| Open AccessAn isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity
Genetic variants in the SBNO2 locus are associated with Crohns’s disease. Here the authors show that those variants cause a cell type and isoform specific effect were transcription of SBNO2 isoform 2 impacts on antimicrobial activity in macrophages providing a plausible gene-mechanism-phenotype model.
- Dominik Aschenbrenner
- , Isar Nassiri
- & Holm H. Uhlig
-
Article
| Open AccessProximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2
Type I IFN is vital for antiviral defense. Here, the authors use TurboID-based proximity labeling to comprehensively map the protein landscapes surrounding core IFN signaling members. Among factors uncovered, PJA2 emerged as a negative regulator of IFN signaling that ubiquitinates the Janus kinases.
- Samira Schiefer
- & Benjamin G. Hale
-
Article
| Open AccessHuman neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head
Here the authors isolate two human antibodies, H7.HK1 and H7.HK2, that achieve broad and potent neutralization against H7N9 influenza by targeting a distinct lateral patch on the hemagglutinin head, thus making them favorable to complement other antibodies for combination therapy.
- Manxue Jia
- , Hanjun Zhao
- & Xueling Wu
-
Article
| Open AccessDeleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Treatment failure following chimaeric antigen receptor (CAR) T cell therapy is common yet incompletely understood. In this study, the authors demonstrate that deletion of the mitochondrial negative regulator, MCJ, in CAR T cells promotes target cell killing ex vivo and augments their efficacy in an in vivo B cell leukaemia model.
- Meng-Han Wu
- , Felipe Valenca-Pereira
- & Mercedes Rincon
-
Article
| Open AccessImmune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer
In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.
- Wolfgang Beckabir
- , Mi Zhou
- & Benjamin G. Vincent
-
Article
| Open AccessAutophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis
Tubulointerstitial inflammation occurs frequently in acute kidney injury (AKI), and Mφ autophagy is a known contributor to inflammation-related diseases. Here, Yuan et al. show that Mφ autophagy deficiency induces systemic inflammation, impairs mitochondria, and worsens kidney injury in AKI mice.
- Yujia Yuan
- , Longhui Yuan
- & Yanrong Lu
-
Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
-
Article
| Open AccessEnteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
The digestive form of Chagas disease (American trypanosomiasis) involves damage to the nervous system of the gastrointestinal tract and problems with peristalsis. Here, Khan et al show that infection causes damage to the colon that can be reversed if it is successfully treated early in the process.
- Archie A. Khan
- , Harry C. Langston
- & Michael D. Lewis
-
Article
| Open AccessHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it’s specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.
- Shixia Wang
- , Kun-Wei Chan
- & Shan Lu
-
Article
| Open AccessDisruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis
Macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is implicated in a range of immunopathology. Here the authors show TIGAR drives inflammation and sepsis via activation of TAK1 and that disruption of TIGAR-TAK1 interaction in a murine model of sepsis reduces immunopathology.
- Dongdong Wang
- , Yanxia Li
- & Jingjing Ben
-
Article
| Open AccessPost-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia
The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia.
- Karen T. Feehan
- , Hannah E. Bridgewater
- & Derek W. Gilroy
-
Article
| Open AccessPriming with LSD1 inhibitors promotes the persistence and antitumor effect of adoptively transferred T cells
Phenotypic changes in exhausted T cells are linked to chromatin remodeling. Here the authors show that pharmacological inhibition of the H3K4me1/2 demethylase LSD1 promotes the persistence and enhances the therapeutic activity of adoptively transferred T cells for cancer therapy.
- Fengqi Qiu
- , Peishan Jiang
- & Wanqiang Sheng
-
Article
| Open AccessIn vivo neutralization of coral snake venoms with an oligoclonal nanobody mixture in a murine challenge model
Oligoclonal mixtures of neutralising antibodies can target multiple antigen components and represent a potential therapeutic solution for the treatment of envenomation. Here, the authors generate mixtures of nanobodies against coral snake venom toxins and demonstrate they can prevent lethality of coral snake venoms in pre-clinical animal models.
- Melisa Benard-Valle
- , Yessica Wouters
- & Andreas Hougaard Laustsen
-
Article
| Open AccessCytomegalovirus drives Vδ1+ γδ T cell expansion and clonality in common variable immunodeficiency
Common variable immunodeficiency (CVID) is an inborn error of immunity, characterized clinically by low immunoglobulin levels, poor vaccine responses and recurrent sinopulmonary infections. Here authors show that the proportion of Vδ1+ γδ T cells in CVID is higher than in healthy controls and these cells respond to persistent cytomegalovirus viremia with expansion and phenotypic alterations.
- Samantha Chan
- , Benjamin Morgan
- & Lauren J. Howson
-
Article
| Open AccessDesigning meaningful continuous representations of T cell receptor sequences with deep generative models
Relating T cell receptor (TCR) sequencing to antigen specificity is a challenge especially when TCR specificity is unclear. Here the authors use a low dimensional generative approach to model TCR sequence similarity and to associate TCR sequences with the same specificity.
- Allen Y. Leary
- , Darius Scott
- & Peter G. Hawkins
-
Article
| Open AccessVascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation
The molecular basis underlying infection infection-mediated lung pathology is not fully revealed. Here the authors report that SPARCL1 expressed in pulmonary capillary endothelial cells contributes to immune pathology in mouse model via pro-inflammatory macrophage induction, while circulating SPARCL1 levels corelate with COVID-19 lethality.
- Gan Zhao
- , Maria E. Gentile
- & Andrew E. Vaughan
-
Article
| Open AccessInvariant γδTCR natural killer-like effector T cells in the naked mole-rat
Naked mole-rats are long-lived rodents known to be resistant to the development of cancer, yet their immune system remains poorly explored. Here, the authors identify natural killer-like effector γδ T cells that express a dominant γδ T cell receptor and may serve a role in tumour immunosurveillance.
- Guillem Sanchez Sanchez
- , Stephan Emmrich
- & David Vermijlen
-
Article
| Open AccessTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Although the function of Toll-like receptor 9 (TLR9) in immunity and inflammation is well-established, its role in obesity is less well-studied. In this study, the authors demonstrate that TLR9 deficiency in B cells is associated with obesity in mice and results in altered frequencies of T and B lymphocyte subsets and gut microbiome dysbiosis.
- Pai Wang
- , Xin Yang
- & Li Wen
-
Article
| Open AccessEnhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Zhenguang Zhang
- , Iain R. L. Kean
- & Nazima Pathan
-
Article
| Open AccessOriginal COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters
Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.
- Luca M. Zaeck
- , Ngoc H. Tan
- & Rory D. de Vries
-
Article
| Open AccessRecruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow
The mechanisms driving B cell differentiation into resident bone marrow plasma cells (BMPC) remain unclear. Here the authors use single cell sequencing and BMPC phenotyping to infer developmental pathways and regulation by IL-21 in germinal centres to promote maintenance of BMPC after vaccination in humans.
- Marta Ferreira-Gomes
- , Yidan Chen
- & Mir-Farzin Mashreghi
-
Article
| Open AccessLong-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment
Tumor-resident intracellular microbiota (TRIM) could be a potential target for anticancer treatment. Here the authors report Au@Ag2Se nano-assemblies enabling bacterial killing, tumor inhibition and immune regulation in tumor microenvironment.
- Yuanlin Wang
- , Yaqian Han
- & Miao Yu
-
Article
| Open AccessSustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.
- Elsa Brunet-Ratnasingham
- , Sacha Morin
- & Daniel E. Kaufmann
-
Article
| Open AccessADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection
Mice lacking A Disintegrin and Metalloproteinase 9 (ADAM9) do not mount Type 1 interferon responses against encephalomyocarditis infection. Here, Bazzone et al show that ADAM9 regulates innate immune responses via by MDA5.
- Lindsey E. Bazzone
- , Junji Zhu
- & Evelyn A. Kurt-Jones
-
Article
| Open AccessCD5L as a promising biological therapeutic for treating sepsis
Authors explore the utility of CD5L for treating experimental sepsis. CD5L deficiency exacerbates experimental sepsis. Conversely, administration of recombinant CD5L in WT mice augments neutrophil function, enhances bacterial control, and mitigates inflammation, leading to substantial improvements in disease outcomes.
- Liliana Oliveira
- , M. Carolina Silva
- & Alexandre M. Carmo
-
Article
| Open AccessOctyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.
- Naziia Kurmasheva
- , Aida Said
- & David Olagnier
-
Article
| Open AccessDouble-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.
- Lucia Montorsi
- , Michael J. Pitcher
- & Jo Spencer
-
Article
| Open AccessPremature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants
Here, Dzanibe et al show that in utero HIV/ARV exposure sequentially disrupts infant immunologic trajectories, beginning with NK cells that predict vaccine antibody responses and followed by delayed T cell memory maturation linked to skewed TCR clonality.
- Sonwabile Dzanibe
- , Aaron J. Wilk
- & Clive M. Gray
-
Article
| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
-
Article
| Open AccessThe structural basis for 2′−5′/3′−5′-cGAMP synthesis by cGAS
Here, the authors provide structural and biochemical data describing the mechanism through which cGAS synthesizes 2′−5′/3′−5′-cGAMP.
- Shuai Wu
- , Sandra B. Gabelli
- & Jungsan Sohn
-
Article
| Open AccessPretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation
Natural killer (NK) cells are assessed for various therapies, but sub-optimal cryopreservation dampens their clinical feasibility. Here the authors show that pretreating human NK cells with IL-15/IL-18 prior to cryopreservation improves NK cell post-thaw viability and functions, potentially via anti-apoptosis gene induction and granzyme B degranulation.
- Abdulla Berjis
- , Deeksha Muthumani
- & Neil C. Sheppard
-
Article
| Open AccessAn integrated technology for quantitative wide mutational scanning of human antibody Fab libraries
Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.
- Brian M. Petersen
- , Monica B. Kirby
- & Timothy A. Whitehead
-
Article
| Open AccessThe STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion
It has been previously suggested that STING agonists can improve response to CAR-T therapy. Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models.
- Ugur Uslu
- , Lijun Sun
- & Carl H. June
-
Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
-
Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
-
Article
| Open AccessCLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation
The NF-kB pathway is strictly regulated to prevent excessive inflammatory and immune responses. Here, Li et al. describe an alternative pathway of negative regulation of p65- driven gene expression.
- Shang-Ze Li
- , Qi-Peng Shu
- & Xiao-Dong Zhang
-
Article
| Open AccessHyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans
Integrin CR3 (CD11b/CD18) is a receptor responsible for recognizing fungal β-glucan. Here, Zhou et al show that the Candida albicans Als family proteins are ligands for the CD11b I domain; an interaction which synergizes with β-glucan to activate CR3.
- Tingting Zhou
- , Norma V. Solis
- & Haoping Liu
-
Article
| Open AccessPD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression
Immune checkpoint inhibition is a successful form of immune therapy; however response rates vary widely among individual patients. Here authors show that circulating small extracellular vesicles might contribute to poor response to anti-PD-1 treatment by carrying PD-1 and CD80 which results in higher level of vesicular PD-L1 expression in the circulation at the expense of expression on tumour cell membranes, causing immunosuppression.
- Lin-Zhou Zhang
- , Jie-Gang Yang
- & Gang Chen
-
Article
| Open AccessTLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Autologous tumor lysate (ATL) dendritic cell (DC) vaccination can induce local and systemic anti-tumor immune responses in malignant glioma patients. In this randomized phase II clinical trial, the authors evaluate the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to ATL-DC vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas.
- Richard G. Everson
- , Willy Hugo
- & Robert M. Prins
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