European Journal of Immunology最新文献

Spatial Multiomics Reveal Insights Into ADC Efficacy. 空间多组学揭示ADC疗效。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70190

Osman Goni, Niklas Klümper, Maria Del Mar Muñiz Moreno, Markus Eckstein, Christoph Kuppe

{"title":"Spatial Multiomics Reveal Insights Into ADC Efficacy.","authors":"Osman Goni, Niklas Klümper, Maria Del Mar Muñiz Moreno, Markus Eckstein, Christoph Kuppe","doi":"10.1002/eji.70190","DOIUrl":"https://doi.org/10.1002/eji.70190","url":null,"abstract":"Antibody-drug conjugates (ADCs) have transformed the therapeutic landscape of solid tumors; however, responses remain heterogeneous and complex to predict. In addition, a growing number of multiple ADC targets are either approved or in late-stage clinical development, such as NECTIN-4, HER2, or TROP2 for metastatic urothelial cancer. Spatial multiomics-representing next-generation methods that couple high-plex RNA sequencing and multiplex protein imaging with precise x-y-z coordinates within tissues-offer a direct way to correlate (ADC) antigen expression, cell state information, and micro-anatomical context with patient treatment outcomes. In this review, we highlight suitability and technological advancements in current spatial transcriptomics and proteomics approaches to decode modes of action and resistance to ADCs and extract biological insights, particularly in metastatic urothelial cancer-and propose an integrative framework that combines spatial readouts with machine and/or deep learning-driven analytics to stratify patients, forecast on- and off-target toxicities, and guide next-generation linker-payload designs or combination therapies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70190"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SYK Signalling in NLRP3 Inflammasome-Mediated Response of Murine Microglia Activated by Immune Complexes Formed of Viral Proteins and Specific IgG. SYK信号在由病毒蛋白和特异性IgG形成的免疫复合物激活的小鼠小胶质细胞NLRP3炎症小体介导的反应中的作用

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70199

Kristina Mašalaitė, Milda Norkienė, Aurelija Žvirblienė, Asta Lučiūnaitė

{"title":"SYK Signalling in NLRP3 Inflammasome-Mediated Response of Murine Microglia Activated by Immune Complexes Formed of Viral Proteins and Specific IgG.","authors":"Kristina Mašalaitė, Milda Norkienė, Aurelija Žvirblienė, Asta Lučiūnaitė","doi":"10.1002/eji.70199","DOIUrl":"https://doi.org/10.1002/eji.70199","url":null,"abstract":"Viral infections might trigger systemic inflammatory responses characterised by inflammasome activation and cytokine release, driven by immune complex (IC) formation, but the precise mechanism remains unknown. The NLRP3 inflammasome is a vital component of innate immunity that plays a significant role in inflammatory responses. The involvement of the non-receptor spleen tyrosine kinase (SYK) in the activation of the NLRP3 inflammasome has been demonstrated. SYK plays a critical role in signal transduction pathways of immunoreceptors and regulates NLRP3 inflammasome activation. Our previous study showed that viral antigens and their IC with specific antibodies trigger NLRP3 inflammasome activation in macrophages. Therefore, we studied the role of SYK in IC-induced NLRP3 inflammasome activation pathway using primary mouse microglia as a macrophage model. The inflammasome activation was analysed by measuring cytokine secretion, ASC speck formation, and NLRP3 expression. To link SYK activation to NLRP3 inflammasome activation and other macrophage functional properties, we employed a specific SYK inhibitor, R406. We demonstrated SYK involvement in NLRP3 inflammasome activation by viral IC and in SYK-dependent antigen presentation in microglia after IC phagocytosis. Our findings also revealed lipid raft clustering upstream of SYK activation. These results may explain the mechanisms behind severe inflammation caused by viral IC.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70199"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Borrelia burgdorferi sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System. 感应伯氏疏螺旋体利用几种逃逸机制绕过人体防御系统。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70195

Zara Karami, Hadewych J M Ter Hofstede, Leo A B Joosten

{"title":"Borrelia burgdorferi sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System.","authors":"Zara Karami, Hadewych J M Ter Hofstede, Leo A B Joosten","doi":"10.1002/eji.70195","DOIUrl":"https://doi.org/10.1002/eji.70195","url":null,"abstract":"Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) through Ixodes tick bites, presents diverse clinical manifestations and may lead to persistent symptoms. This review summarizes current knowledge on the pathogen-host interactions and immune responses. Early infection can be influenced by tick saliva, which suppresses local host defense and promotes spirochete survival, and by pattern recognition receptors activating proinflammatory cascades. Bbsl employs a variety of immune evasion strategies, notably impairing antigen presentation-through disruption of MHC II and IFN-γ pathways-and continuously varying surface antigens to hinder long-lasting antibody formation. Autophagy plays a central role in modulating inflammation and T helper 17 adaptive immune responses, representing an underappreciated mechanism potentially influencing disease outcome. Adaptive immunity in LB is characterized by robust but often dysregulated humoral and cellular responses, with transient germinal centers and enduring IgM production contributing to incomplete pathogen clearance. Persistent immune defects include impaired long-term B cell memory, suppressed T cell activation, and ongoing immunosuppression after pathogen clearance. Similar patterns are observed in other postinfectious fatigue syndromes. Despite advances, gaps remain in understanding mechanisms of Bbsl persistence and the immunopathology underlying chronic disease, challenging diagnosis and therapy. Emerging molecular and cellular approaches offer new avenues to address immunity, diagnostics, and prevention. A multidisciplinary effort will be needed to improve long-term patient outcomes in the evolving epidemiology of LB.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70195"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adapted Live SARS-CoV-2 Vaccine Elicits Rapid Mucosal Immunity, Protects From Disease, and Reduces Shedding of XBB.1.5. 适应的SARS-CoV-2活疫苗可引发快速粘膜免疫，预防疾病，并减少XBB.1.5的脱落

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70196

Jana Kochmann, Tobias Britzke, Nico Joël Halwe, Lorenz Ulrich, Angele Breithaupt, G Tuba Barut, Nadine Ebert, Bettina Salome Trüeb, Volker Thiel, Anca Dorhoi, Martin Beer, Donata Hoffmann, Björn Corleis, Jacob Schön

{"title":"Adapted Live SARS-CoV-2 Vaccine Elicits Rapid Mucosal Immunity, Protects From Disease, and Reduces Shedding of XBB.1.5.","authors":"Jana Kochmann, Tobias Britzke, Nico Joël Halwe, Lorenz Ulrich, Angele Breithaupt, G Tuba Barut, Nadine Ebert, Bettina Salome Trüeb, Volker Thiel, Anca Dorhoi, Martin Beer, Donata Hoffmann, Björn Corleis, Jacob Schön","doi":"10.1002/eji.70196","DOIUrl":"https://doi.org/10.1002/eji.70196","url":null,"abstract":"The emergence of SARS-CoV-2 variants, like XBB.1.5, causing immune evasion and frequent breakthrough infections, emphasizes the need for vaccines that limit transmission and target newly emerging variants. Mucosal vaccines, particularly live attenuated vaccines (LAV), are promising candidates for inducing strong mucosal immune responses to prevent viral replication and transmission. Vaccination with the previously described \"one-to-stop\" codon-modified LAV OTS-228, carrying the ancestral spike protein, induced sterilizing immunity against ancestral SARS-CoV-2 but also broad protection against Omicron variants, including XBB.1.5, but transmission of XBB.1.5 to contacts could not be prevented completely. As a proof-of-concept, we updated OTS-228 by replacing the sequence coding for the ancestral SARS-CoV-2 spike protein with that of the XBB.1.5 variant. We applied flow cytometry to detect SARS-CoV-2-specific T cell responses, as well as ELISA and qPCR, to characterize systemic and mucosal immune responses in Syrian hamsters in detail. The new OTS construct designated as \"OTS-300\" exhibited an optimal safety profile in Syrian hamsters comparable to the original candidate vaccine. A single-dose intranasal (i.n.) vaccination with OTS-300 protects against disease, substantially limits XBB.1.5 replication, and reduces transmission in Syrian hamsters, showcasing the adaptability of the OTS platform for other emerging variants. OTS-300 induced accelerated mucosal and systemic antibody responses and reduced virus-mediated inflammation as compared with an intramuscularly delivered mRNA vaccine encoding the XBB.1.5 Spike.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70196"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Deletion of Lymphatic PD-L1 Protects Mice From Severe Autoimmune Encephalitis". 更正“淋巴PD-L1缺失保护小鼠免受严重自身免疫性脑炎”。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70203

引用次数: 0

CD8 T Cell Sensing of Type I Interferon Impacts Anergy. CD8 T细胞感知I型干扰素对能量的影响。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70192

Anne S Haefke, Hanna Gröber, Ioana Sandu, Vanessa Skipness, Nikos Pantouloufos, Fabienne Gräbnitz, Marie-Elen Tuchel, Nathan Zangger, Dominique Stark, Marvin Kříž, Carmine Cristinzio, Hanspeter Pircher, Roman Spörri, Isaak Quast, Annette Oxenius

{"title":"CD8 T Cell Sensing of Type I Interferon Impacts Anergy.","authors":"Anne S Haefke, Hanna Gröber, Ioana Sandu, Vanessa Skipness, Nikos Pantouloufos, Fabienne Gräbnitz, Marie-Elen Tuchel, Nathan Zangger, Dominique Stark, Marvin Kříž, Carmine Cristinzio, Hanspeter Pircher, Roman Spörri, Isaak Quast, Annette Oxenius","doi":"10.1002/eji.70192","DOIUrl":"10.1002/eji.70192","url":null,"abstract":"Peripheral tolerance is indispensable for the maintenance of immune homeostasis, allowing protective immunity while limiting responses to self-antigens. CD8 T cells activated in the absence of co-stimulation and pro-inflammatory cytokines are either deleted, rendered anergic, or actively suppressed. These mechanisms are well established, but the cues determining the mode and depth of peripheral tolerance remain incompletely understood. Here, we identify type I interferon (IFN-I) signalling in T cells as a key modulator of peripheral tolerance in the absence of infection. In the complete absence of IFN-I signalling, autoreactive CD8 T cells are rendered anergic, and their expansion, phenotype and function are tightly controlled. Basal levels of IFN-I are sufficient for self-reactive CD8 T cells to expand and retain partial effector functions in the absence of viral infections. This is dependent on T cell-intrinsic IFN-I sensing and is associated with the generation of a partially anergic, TCF1+ CD8 T cell subset that can contribute to a pathogen-specific immune response. Collectively, our results suggest that elevated basal IFN-I levels limit anergy induction, providing a potential mechanistic explanation for the association of baseline inflammation with the development of autoimmunity.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70192"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mapping of Neutrophils in Cancers: Insights From Spatial Omics Technologies. 中性粒细胞在癌症中的定位：来自空间组学技术的见解。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70194

Xiaohe Li, Xi He, Shan Cao, Changming Shih, Xiaoxiang Chen, Lai Guan Ng

{"title":"Mapping of Neutrophils in Cancers: Insights From Spatial Omics Technologies.","authors":"Xiaohe Li, Xi He, Shan Cao, Changming Shih, Xiaoxiang Chen, Lai Guan Ng","doi":"10.1002/eji.70194","DOIUrl":"https://doi.org/10.1002/eji.70194","url":null,"abstract":"Tumor neutrophils exhibit marked phenotypic plasticity and can play dual roles in tumor biology, encompassing both tumor-promoting and tumor-suppressive activities. Single-cell RNA sequencing (scRNA-seq) enables transcriptomic profiling of tumor neutrophils at single-cell resolution, whereas spatial transcriptomics (ST) addresses key limitations of scRNA-seq by preserving the spatial context of cells within intact tissue, thereby minimizing cell loss and maintaining native tissue architecture. As ST technology continues to advance, it offers increasingly comprehensive insights into the regulatory mechanisms of tumor neutrophils within the tumor microenvironment (TME). In this review, we first summarize recent technological advancements in ST. We then discuss neutrophil detection across various cancer types, highlighting key differences and challenges in neutrophil research across studies and malignancies. Furthermore, we outline recommendations for sequencing strategies and sample processing to optimize the study of tumor neutrophils. Finally, we highlight that integrating ST with multi-omics approaches offers a promising avenue to advance our understanding of tumor neutrophil biology and to identify more precise biomarkers for targeted therapies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70194"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unfavourable H-CDR3 Loops in preB Cells Lead to Highly Expanded Plasma Cell Clones. preB细胞中不利的H-CDR3环导致浆细胞克隆高度扩增。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-05-01 DOI: 10.1002/eji.70200

Alaitz Aranburu, Erik Engström, Erik Demitz-Helin, Julia M Scheffler, Alessandro Camponeschi, Timothy Sundell, Zhong Ni, Inga-Lill Mårtensson

{"title":"Unfavourable H-CDR3 Loops in preB Cells Lead to Highly Expanded Plasma Cell Clones.","authors":"Alaitz Aranburu, Erik Engström, Erik Demitz-Helin, Julia M Scheffler, Alessandro Camponeschi, Timothy Sundell, Zhong Ni, Inga-Lill Mårtensson","doi":"10.1002/eji.70200","DOIUrl":"10.1002/eji.70200","url":null,"abstract":"The immune system is essential for protection against invading pathogens. However, if it fails to distinguish between non-self (pathogens) and self, autoimmunity can result. B cells recognise pathogens using their B-cell antigen receptor (BCR), a membrane-bound antibody. The variable region of the BCR contacts antigens via complementarity-determining regions (CDRs). This region is encoded by immunoglobulin (Ig) V(D)J gene segments, which are randomly recombined during B-cell development. Failure to counter-select unfavourable H-CDR3s is considered an underlying feature of autoimmunity. Here, we examined the effect of impaired pre-BCR selection on plasma cells (PCs) using a model of autoimmunity characterised by elevated serum autoantibody levels. Our results demonstrate that the absence of a pre-BCR leads to an increase in H-CDR3s that are translated into unfavourable reading frames, encoding highly hydrophobic and/or basic amino acid residues, including a subset with extremely short H-CDR3s. These features are not fully corrected by Ig light chains and persist in mature B cells. Ultimately resulting in the massive clonal expansion of PCs expressing a repertoire skewed towards extremely short H-CDR3s that contain highly hydrophobic and/or positively charged residues. Consequently, preB cells with unfavourable H-CDR3 features lead to the expansion of autoreactive PCs with the same features.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 5","pages":"e70200"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased Constitutive Interferon-β Levels and Altered CD4 T Cell Homeostasis Induced by Expression of a Viral Glycoprotein 一种病毒糖蛋白表达诱导的组成型干扰素-β水平升高和CD4 T细胞稳态改变

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-13 DOI: 10.1002/eji.70188

Hanspeter Pircher, Oliver S. Thomas, Anne S. Haefke, Annette Oxenius, Thomas Boehm

{"title":"Increased Constitutive Interferon-β Levels and Altered CD4 T Cell Homeostasis Induced by Expression of a Viral Glycoprotein","authors":"Hanspeter Pircher, Oliver S. Thomas, Anne S. Haefke, Annette Oxenius, Thomas Boehm","doi":"10.1002/eji.70188","DOIUrl":"10.1002/eji.70188","url":null,"abstract":"Besides the strong Type I interferon (IFN-I) response induced by infections, IFN-I is also produced constitutively at lower levels. Constitutive IFN-I production is regulated by resident microbiota and is essential for induction of efficient immune responses. Here, we demonstrate in transgenic (tg) mice that expression of a single viral envelope gene, the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), increased constitutive IFN-β levels and induced numerous IFN-stimulated genes (ISGs). In addition, self-antigen-driven CD44highCD62Llow memory-phenotype CD4 T cells and regulatory CD4 T cell populations were enlarged in these LCMV GP-tg mice; by contrast, the fraction of bona fide antigen-specific memory CD4 T cells remained unchanged. Our study demonstrates that expression of a single viral envelope gene increased constitutive IFN-β levels, induced upregulation of ISGs, and altered CD4 T cell homeostasis. Our results further suggest that a hitherto undefined signaling pathway capable of inducing IFN-β expression can detect LCMV GP at the protein or transcript level.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uncovering Immune Niches in Health and Disease Using Spatial Transcriptomics 利用空间转录组学揭示健康和疾病中的免疫生态位。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2026-04-07 DOI: 10.1002/eji.70185

Johan Thorsson, Yang Zhao, Eduardo J. Villablanca, Camilla Engblom

引用次数: 0