Featured
-
-
Article
| Open AccessCis-regulatory evolution of the recently expanded Ly49 gene family
The Ly49 gene family mainly encodes inhibitory or activating surface receptors on natural killer cells. Here the authors show that in mice, inhibitory and activating Ly49 genes are regulated by two distinct sets of cis-regulatory elements, and that different Ly49 genes can be cross-regulated.
- Changxu Fan
- , Xiaoyun Xing
- & Ting Wang
-
Article
| Open AccessKSHV infection of B cells primes protective T cell responses in humanized mice
Kaposi sarcoma associated herpesvirus (KSHV) and Epstein Barr virus often co-infect hosts and some malignancies, such as primary effusion lymphoma, are typically arising from dual-infected cells. Here authors recapitulate dual infection in a humanized mouse model, and find that under these conditions, an efficient and specific CD8+ T cell response is mounted against the lytic KSHV antigen K6.
- Nicole Caduff
- , Lisa Rieble
- & Christian Münz
-
Article
| Open AccessUltrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas
Ultrasound-mediated blood-brain barrier opening has been exploited to improve drug delivery in the brain. Here the authors show that low-intensity pulsed ultrasound in combination with intravenous injection of microbubbles enhances the delivery of doxorubicin and anti-PD1 in gliomas, improving anti-tumor immune responses.
- Víctor A. Arrieta
- , Andrew Gould
- & Adam M. Sonabend
-
Article
| Open AccessMicrobiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation
The epigenetic program underlying the differentiation of innate lymphoid cell precursors (ILCPs) into innate lymphoid cell (ILC) subsets remains poorly understood. Here the authors show genome-wide distribution of the DNA methylation and hydroxymethylation in murine ILC subsets and at postnatal stage, gut microbiota contributes to the downregulation of TET1 level, resulting in an expansion of ILC1s.
- Xusheng Zhang
- , Xintong Gao
- & Shuo Wang
-
Article
| Open AccessBurkholderia pseudomallei BipD modulates host mitophagy to evade killing
The selective degradation of mitochondria by autophagy is essential for cell homeostasis. Here, Nan et al show that the effector protein BipD, secreted by Burkholderia pseudomallei, is able to modulate host mitophagy to promote its survival.
- Dongqi Nan
- , Chenglong Rao
- & Qian Li
-
Article
| Open AccessSphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α
Non-alcoholic steatohepatitis has with few well-defined biomarkers or clinically effective treatments but is promoted by inflammation. Here, the authors find an active lipid [So(d18:1)] that is significantly changed in patients and promotes inflammation by directly inhibiting macrophage HIF-2α.
- Jialin Xia
- , Hong Chen
- & Yanli Pang
-
Article
| Open AccessGeneration of nanobodies from transgenic ‘LamaMice’ lacking an endogenous immunoglobulin repertoire
Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.
- Thomas Eden
- , Alessa Z. Schaffrath
- & Friedrich Koch-Nolte
-
Article
| Open AccessIL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice
The use of CTLA4-Ig fusion proteins in transplantation remains limited due to co-stimulation blockade-resistant rejection (CBRR). In this study, the authors demonstrate that IL-6 blockade reduces CBRR in murine cardiac transplants in the context of T cell-depleting induction regimens and CTLA4-Ig treatment.
- Moritz Muckenhuber
- , Konstantinos Mengrelis
- & Thomas Wekerle
-
Article
| Open AccessAnti-PD-1 cis-delivery of low-affinity IL-12 activates intratumoral CD8+T cells for systemic antitumor responses
IL-12 has been shown to enhance the efficacy of anti-PD-1 therapy, but this has been hampered by issues with toxicity and poor delivery to the tumour site. In this study, the authors generate an anti-PD-1 antibody/IL-12 fusion protein for specific targeting of IL-12 to tumour sites, resulting in potent anti-tumour immunity with limited toxicity.
- Zhuangzhi Zou
- , Jiao Shen
- & Hua Peng
-
Article
| Open AccessNeutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure
This study reports training by lipopolysaccharide to expand neutrophils expressing the anti-bacterial galectin-3 protein defending mice from a lethal bacterial infection, a similar signature associated with survivors of respiratory failure in humans.
- Sudipta Das
- , Tomasz W. Kaminski
- & Prabir Ray
-
Article
| Open AccessPulmonary maternal immune activation does not cross the placenta but leads to fetal metabolic adaptation
Maternal immune activation during pregnancy can negatively impact the developing fetus. Here, applying multi-omics (RNA-seq, phosphoproteomics and lipidomics) and imaging, the authors show that while maternal immune activation induces strong innate response in maternal organs it does not extend through the placenta but leads to fetal metabolic changes.
- Signe Schmidt Kjølner Hansen
- , Robert Krautz
- & Albin Sandelin
-
Article
| Open AccessPeripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development
Self-tolerance is established during B cell development but the contribution of clonal deletion, receptor editing, anergy and apoptosis is debated. Here we show that although apoptosis does occur in a high proportion of transitional B cells after exiting the bone marrow, the reactivity of apoptotic B cells does not differ from that of viable cells, which argues against apoptosis as major mechanism to eliminate self-reactive and polyreactive clones.
- Mikala JoAnn Simpson
- , Anna Minh Newen
- & Christian Thomas Mayer
-
Article
| Open AccessInherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans
Variants of the 3′−5′ exonuclease TREX1 can cause retinal vasculopathy with cerebral leukoencephalopathy (RVCL). Here, the authors show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and render cells more vulnerable to DNA damage inducing agents.
- Samuel D. Chauvin
- , Shoichiro Ando
- & Jonathan J. Miner
-
Article
| Open AccessGlycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy
Central memory CD8+ T cells (Tcm) are important for lasting anti-tumour immunity and their differentiation is determined by underpinning transcriptional and metabolic regulation. Authors here show that although microwave ablation (MWA) cancer therapy induces T cells to acquire some of the gene expression features of Tcms, but the full metabolic remodeling required for functionality is only achieved if glycolysis is inhibited simultaneously.
- Xinyu Tang
- , Xinrui Mao
- & Wenbin Zhou
-
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
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