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Article
| Open AccessLSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model
Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.
- Alberto Díez-Sánchez
- , Håvard T. Lindholm
- & Menno J. Oudhoff
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Article
| Open AccessAn ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation
Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.
- Seoryeong Park
- , Jaewon Choi
- & Junho Chung
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Article
| Open AccessAn esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease.
- Jiarui Ding
- , John J. Garber
- & Ramnik J. Xavier
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Article
| Open AccessConsistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Xenotransplantation is an imminent clinical reality but concerns remain around the logistics of procurement and the experimental immunosuppression regimens required to achieve long-term xenograft survival. Here the authors show more than 6 month survival of genetically modified porcine kidneys in baboons after regulatory compliant organ procurements, clinically relevant organ preservation times and FDA-approved immunosuppressive reagents.
- Daniel Eisenson
- , Yu Hisadome
- & Kazuhiko Yamada
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Article
| Open AccessAntiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.
- Michael D. Keller
- , Patrick J. Hanley
- & Michael A. Pulsipher
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Article
| Open AccessImpact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering
Concerns over the immunogenicity of poly(ethylene glycol) (PEG) are growing, and the implications for tissue engineering are unknown. Here the authors evaluate the impact of anti-PEG antibodies and PEG immunogenicity on the efficacy of a PEG hydrogel-based tissue engineering therapy.
- Alisa H. Isaac
- , Sarea Y. Recalde Phillips
- & Daniel L. Alge
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Article
| Open AccessInflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants
HIV exposed but uninfected infants may face an increased risk of serious infection and mortality. In this work, the authors utilise a cohort from rural Zimbabwe to explore the biological mechanisms underlying infant mortality.
- Ceri Evans
- , Kuda Mutasa
- & Andrew J. Prendergast
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Article
| Open AccessImprovement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection
Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.
- Chansavath Phetsouphanh
- , Brendan Jacka
- & Gail V. Matthews
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Article
| Open AccessEmerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Many emerging SARS-CoV-2 variants partially escape the humoral immune response. Here, Liu et al. characterize 28 antibodies from BA.4/5 breakthrough infections and find attrition of neutralization and complete loss of function for variants with Spike mutations at positions 455 and 456.
- Chang Liu
- , Raksha Das
- & Gavin R. Screaton
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Article
| Open AccessCXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis
Here, the authors demonstrate that CXCL5 expression is increased in ankle joints of gouty arthritis model mice. CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and joint inflammation.
- Chengyu Yin
- , Boyu Liu
- & Boyi Liu
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Article
| Open AccessDonor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease
Graft-versus-Host disease is a major complication after allogeneic bone marrow transplantation and is ameliorated by adoptively transferred donor regulatory T cells. Here, the authors apply transcriptomic and TCR profiling to assess regulatory T cell organ-specific adaptation in murine bone marrow transplantation models.
- David J. Dittmar
- , Franziska Pielmeier
- & Michael Rehli
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Article
| Open AccessDeep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells
Prediction of the specificity of a T cell receptor from amino acid sequence has been performed using different methods and approaches. Here the authors use TCRab sequences with known specificity to develop a deep learning TCR-epitope interaction predictor and use this method to predict specificity of dual alpha chain TCRs and TCRs specific for different antigens.
- Giancarlo Croce
- , Sara Bobisse
- & David Gfeller
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Article
| Open AccessInfluenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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Article
| Open AccessA plant NLR receptor employs ABA central regulator PP2C-SnRK2 to activate antiviral immunity
Huang et al. show how plant Sw-5b NLR mimics the ABA receptor to activate ABA-dependent antiviral immunity via the PP2C-SnRK2 complex. They reveal that Sw-5b NLR induces ABA accumulation, upregulates ABA response genes, and triggers defense against viral infections by releasing SnRK2 from PP2C inhibition.
- Shen Huang
- , Chunli Wang
- & Xiaorong Tao
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Article
| Open AccessSemmaphorin 3 A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells
Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8+ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8+ T cell migration and function.
- Mike B. Barnkob
- , Yale S. Michaels
- & Vincenzo Cerundolo
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Article
| Open AccessSystematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
The design of new combinatorial regimens represents an opportunity to improve response to immune checkpoint inhibitors in patients with cancer. Here the authors computationally model the interaction between chemotherapy and immunotherapy by studying treatment-induced expression changes associated with response to anti-PD-1, identifying chemotherapeutic drugs or small molecule inhibitors that can overcome resistance to anti-PD-1.
- Yue Wang
- , Dhamotharan Pattarayan
- & Da Yang
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Article
| Open AccessSpatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant
Xenotransplantation in humans using pig organs could improve the transplant organ supply. Here the authors transplant pig kidneys into a brain-dead recipient and monitor the human immune cell response early after transplantation using spatial and single cell transcriptomics and show early myeloid cell infiltration.
- Matthew D. Cheung
- , Rebecca Asiimwe
- & Paige M. Porrett
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Article
| Open AccessCoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits
HIV vaccine candidates often have limited capacity to induce broadly neutralizing antibodies (nAbs). In this study, the authors show that stabilized Clade C HIV-1 Env protein trimers decorated on CoPoP liposomes induce nAbs against 18 of 20 multiclade tier 2 HIV-1 strains in immunized rabbits.
- Annemart Koornneef
- , Kanika Vanshylla
- & Frank Wegmann
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Article
| Open AccessEvolution of T cells in the cancer-resistant naked mole-rat
Naked mole-rats are long-lived rodents with remarkable resistance to cancer. Here authors show that their T-cell compartment is different from that of mice in that they have a large population of circulating cytotoxic γδ T cells harboring a dominant clonotype, and the clonotypic diversity of their conventional cytotoxic αβ T cells is more modest than that of mice.
- Tzuhua D. Lin
- , Nimrod D. Rubinstein
- & Rochelle Buffenstein
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Article
| Open AccessEarly-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice
Exercise could affect the immune system, but whether early-life exercise could benefit immune health in adulthood is not fully understood. Here the authors show that early-life exercise promotes epi-metabolic changes in the liver to potentially benefit immunity in older age and characterise the involvement of pipecolic acid in this process.
- Nini Zhang
- , Xinpei Wang
- & Feng Gao
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Article
| Open AccessVaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin
Immune imprinting can affect the response to future infection with pathogen variants. Here, Pušnik et. al. demonstrate that previous vaccination with wild-type SARS-CoV-2 vaccine hampers the formation of an immune response to mutated regions of omicron surface proteins following omicron breakthrough infection.
- Jernej Pušnik
- , Jasmin Zorn
- & Hendrik Streeck
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Article
| Open AccessImmunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
In this study, Giron et al. find that people living with chronic HIV experience accelerated aging-associated alterations in antibody glycans. These alterations, attributed to senescence enzymes, predict comorbidities and reduce the antiviral function of antibodies.
- Leila B. Giron
- , Qin Liu
- & Mohamed Abdel-Mohsen
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Article
| Open AccessAntigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis
Although many autoimmune diseases are characterized by the presence of autoantibodies, complete characterisation of autoantibody repertoires is lacking. Here, the authors introduce an autoantigen-specific Fab profiling method to show that the autoantibody repertoire in rheumatoid arthritis is diverse yet dominated only by a few clones.
- Eva Maria Stork
- , Danique M. H. van Rijswijck
- & Albert Bondt
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Article
| Open AccessSARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals
Prior infection or exposure to SARS-CoV-2 may influence immunogenicity and effectiveness of subsequent vaccination to new strains of virus. Here the authors show that immunogenicity of a BA.4/5 mRNA vaccine differed in recipients depending on whether they had been exposed to or infected with an earlier strain of virus.
- Rebecca Urschel
- , Saskia Bronder
- & Martina Sester
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Article
| Open AccessDHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Inflammatory bowel disease (IBD) is featured with epithelial barrier dysfunction, however, the underlying mechanism is less clear. Here, the authors show that DHX9 deficiency in intestinal stem cells (ISCs) induces accumulation of abnormal R-loops and subsequent genomic instability, leading to impairment of ISCs and development of IBD.
- Xingxing Ren
- , Qiuyuan Liu
- & Shu Zhu
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Article
| Open AccessDermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice
The microbial community in the intestine can affect other organs such as the skin but it is not clear if the opposite can occur. Here the authors show that skin wounding affects the microbial composition of the intestinal flora which then enhances DSS induced colitis and intestinal inflammation.
- Tatsuya Dokoshi
- , Yang Chen
- & Richard L. Gallo
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Article
| Open AccessA live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections
Authors utilise a murine model of Escherichia coli infection to immunologically characterise the properties of their live attenuated vaccine candidate. They also demonstrate protection of newborn mice following maternal immunisation.
- Youssouf Sereme
- , Cécile Schrimp
- & David Skurnik
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Article
| Open AccessExtracellular DNA traps in a ctenophore demonstrate immune cell behaviors in a non-bilaterian
Identifying core mechanisms of immune cells is critical for understanding the evolution of animal immune function. Here, Vandepas et al. report that ctenophore immune-like cells release extracellular DNA traps when exposed to microbes.
- Lauren E. Vandepas
- , Caroline Stefani
- & Adam Lacy-Hulbert
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Article
| Open AccessPhage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model
Bacteriophage can be used to target bacterial infection and used as a therapeutic approach for antibiotic resistant bacteria. Here the authors show that the use of bacteriophage to target antibiotic resistant bacteria in a mouse model of infection can induce phage specific immune responses and may impair their therapeutic efficacy.
- Julia D. Berkson
- , Claire E. Wate
- & Paul E. Carlson Jr.
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Article
| Open AccessPotent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains
Nipah virus is a WHO priority pathogen, and there is currently no approved drug for clinical therapy. Here, the authors identified potent human neutralizing antibodies that block receptor binding and provide protection against NiV infection in vivo.
- Li Chen
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessSenescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice
In their previous study, the researchers systematically revealed that endplate sclerosis is a significant aspect of spine degeneration or aging and a primary source of spinal pain. However, the underlying mechanisms of endplate sclerosis remained unclear. In their current report, it is shown that senescent cells accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging mouse models. The clearance of these senescent cells was found to restrain angiogenesis coupled with endplate sclerosis. Notably, macrophages were identified as undergoing senescence in the sclerotic endplates. The specific knockout of cdkn2a (p16) in macrophages abrogated LSI or aging-induced angiogenesis and sclerosis in the endplates. Moreover, both in vivo and in vitro studies indicated that IL-10 mediates the effects of senescent macrophages on angiogenesis and sclerosis in the endplates. Overall, these findings suggest that senescent macrophages orchestrate angiogenesis coupling with endplate sclerosis via the IL-10/pSTAT3 axis. This study enhances the understanding of the connection between immune senescence and endplate sclerosis and uncovers senescent macrophage-initiated endplate sclerosis as potential therapeutic targets for spinal degeneration.
- Yonggang Fan
- , Weixin Zhang
- & Shuangfei Ni
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Article
| Open AccessDevelopmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation
The heterogeneity in naive CD8+ T cells is essential for diverse immune responses. Here the authors show that variations in developmental self-reactivity of CD8+ T cells influence their differentiation into Tc17 cells in inflammatory conditions.
- Gil-Woo Lee
- , Young Ju Kim
- & Jae-Ho Cho
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Article
| Open AccessMonoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
Effective antibodies targeting various respiratory syncytial virus (RSV) proteins are needed to address public health burden of RSV. Here the authors shows that in addition to the currently approved F-targeting monoclonal antibodies, anti-G cross-reactive monoclonal antibodies to RSV-A and RSV-B strains can provide cross-protection and prevent from RSV disease.
- Youri Lee
- , Laura Klenow
- & Surender Khurana
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Article
| Open AccessLoss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment
CREBBP and KMT2D mutations frequently co-occur in B cell lymphomas with unclear significance. Here the authors show that they cooperate to skew B cell fate decisions and induce a CD8-depleted immune-evasive microenvironment to facilitate lymphomagenesis.
- Jie Li
- , Christopher R. Chin
- & Ari M. Melnick
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Article
| Open AccessDupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells
Dupilumab-associated head and neck dermatitis has been described in a subset of patients treated with the IL4R-blocker dupilumab. Here the authors characterise the immune cell composition and single-cell transcriptome in comparison with untreated forms of atopic dermatitis in a small cohort showing increases in IL-22-associated genes.
- Christine Bangert
- , Natalia Alkon
- & Patrick M. Brunner
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Article
| Open AccessA commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response
Faecal microbiome transplant has been shown to be able to reduce Clostridioides difficile infection. Here the authors show that an intestinal commensal protozoan reduces C. difficile infection by inhibiting neutrophil recruitment and affecting arginine-ornithine metabolism.
- Huan Yang
- , Xiaoxiao Wu
- & Bing Gu
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Article
| Open AccessObesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk
Obesity represents a risk factor for cancer and compromises immune function, however the mechanisms linking the two together are not fully known. Here authors show in a mouse sarcoma model that obesity increases tumour incidence, impairs intra-tumoral T cell immunity but paradoxically increases sensitivity to immune therapy via impairing immunoediting.
- Alexander Piening
- , Emily Ebert
- & Ryan M. Teague
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Article
| Open AccessDysregulation of Wnt/β-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells
RORγt+ group 3 innate lymphoid cells are intimately involved in intestinal homeostasis, their dysregulation is linked to inflammatory gut diseases. Here the authors show that dysregulated Wnt/β-catenin signalling contributes to disturbed regulation of group 3 innate cells and intestinal inflammation.
- Jiacheng Hao
- , Chang Liu
- & Xiaohuan Guo
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Article
| Open AccessCD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer
Tumor associated macrophages (TAM) are playing an active role in tumor immune evasion in multiple cancer type. Here authors show that CD276 expression by TAMs may underpin this immune-suppressive role via promoting efferocytosis and suppressing MHC class II expression, which result in decreased CD4+ and CD8 + T cell infiltration.
- Maosheng Cheng
- , Shuang Chen
- & Liang Peng
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Article
| Open AccessPCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor
Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to an increase of LDL cholesterol in blood. Here the authors show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor.
- Dasom Shin
- , Soungchan Kim
- & Hyo-Soo Kim
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Article
| Open AccessMyeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies
Myeloid derived suppressor cells (MDSC) are associated with tumourigenesis and therapy response. Here, the authors show that beta 2-adrenergic receptor activation in MDSC leads to metabolic rewiring which regulates chemotherapy response in preclinical models of blood cancer.
- Saeed Daneshmandi
- , Jee Eun Choi
- & Hemn Mohammadpour
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Article
| Open AccessGasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation
Gasdermin D (GSDMD) is a pore forming protein activated by inflammasome derived caspases. Here the authors characterize the function of GSDMD in mouse influenza virus infection and show that immunopathology is reduced in the absence of GSDMD and involves changes in neutrophil function.
- Samuel Speaks
- , Matthew I. McFadden
- & Jacob S. Yount
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Article
| Open AccessSecondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication
Infusion of virus-specific T (VST) cells is used for treating drug-resistant viremia. Here the authors report, as part of the clinical trial, NCT03475212, a lethal case of unexpected bone marrow graft loss and chimerism reversal that is induced by the infusion of third-party VST intended to treat transplantation-related cytomegalovirus viremia.
- Michael D. Keller
- , Stefan A. Schattgen
- & Catherine M. Bollard
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Article
| Open AccessImmunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients
SARS-CoV-2 immune responses after vaccination in individuals with multiple sclerosis (MS) remain poorly understood. Here, using mass cytometry, the authors demonstrate that, following three doses of mRNA vaccine, patients with MS have distinct metabolic profiles in antigen-specific B and T cells.
- Sara De Biasi
- , Domenico Lo Tartaro
- & Andrea Cossarizza
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Article
| Open AccessCholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds
Cholesterol lowering medication positively affects anti-cancer immune response, but the underpinning mechanism is not fully known. Here authors show that the effect is mediated by specific cholesterol binding motifs in STING, a key mediator of inflammation, via regulating its trafficking to Golgi.
- Bao-cun Zhang
- , Marlene F. Laursen
- & Martin R. Jakobsen
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Article
| Open AccessAutophagy-enhancing ATG16L1 polymorphism is associated with improved clinical outcome and T-cell immunity in chronic HIV-1 infection
T cell dysregulation is a hallmark of chronic HIV-1 infection that is partially restored by antiretroviral therapy. Here the authors show that ATG16L1 rs6861 polymorphism is associated clinically with prolonged control of disease pathogenesis, and functionally with enhanced autophagy and T-cell immunity in chronically HIV-1 infected individuals.
- Renée R. C. E. Schreurs
- , Athanasios Koulis
- & Carla M. S. Ribeiro
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Article
| Open AccessThe IL-33/ST2 axis is protective against acute inflammation during the course of periodontitis
Current animal models of periodontitis are biased towards sample collection from gingival tissue, while other periodontal structures may play similarly important role in the initiation and maintenance of inflammation. Here authors present a model that enables a more comprehensive and longitudinal assessment of periodontal tissues, which points to a pivotal role for the peri-root tissues and an IL-33/ST2 axis in the pathogenesis.
- Anhao Liu
- , Mikihito Hayashi
- & Tomoki Nakashima
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Article
| Open AccessThe SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86
Due to the focus of vaccination on the SARS CoV-2 spike protein, spike has been associated with high levels of viral mutation and subsequent immune escape. Here the authors study a conserved epitope in SARS CoV-2 sub-domain-1 and characterise the neutralising antibody response and evasion in contemporary SARS COV-2 viral strains.
- Daming Zhou
- , Piyada Supasa
- & Gavin R. Screaton
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Article
| Open AccessRegulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus
Systemic Lupus Erythematosus (SLE) is a chronic and progressive autoimmune disease characterized by abnormally activated B cells causing organ damage. Here authors introduce an adoptive cell therapy involving regulatory T cells overexpressing FoxP3 and harboring an anti-CD19 CAR to inhibit pathological B cells and thus tissue-harming autoimmunity in a humanized mouse model.
- M. Doglio
- , A. Ugolini
- & C. Bonini
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