European Journal of Immunology最新文献

{"title":"Issue Information: Eur. J. Immunol. 4'26","authors":"","doi":"10.1002/eji.70183","DOIUrl":"10.1002/eji.70183","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585108","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}

{"title":"Going Virtual as a Memory-Phenotype T Lymphocyte","authors":"Bin Yang,&nbsp;Benjamin G. Dewals","doi":"10.1002/eji.70174","DOIUrl":"10.1002/eji.70174","url":null,"abstract":"<p>Conventional or ‘true’ memory CD8⁺ T cells (T_TM) arise from immunologically naive T cells that circulate in the periphery after selection in the thymus. During infection or immunization by a foreign antigen, naive T cells can receive antigen-specific activation signals after recognition of MHC-antigenic peptide complexes. But the CD8⁺ T-cell population in immunologically naive hosts is not restricted to circulating naive T cells expecting cognate antigen encounter. Indeed, memory-phenotype T cells (T_MP) develop in the absence of foreign antigen encounter and therefore exist in naive, pathogen-free, as well as germ-free conditions. T_MP have been shown to mediate bystander cell killing through innate mechanisms, as well as rapidly respond to cognate antigen stimulation. While the existence of foreign antigen-inexperienced T_MP is now well acknowledged in laboratory mice, and also recognized in humans, the extensive nomenclature used for their description challenges the overall understanding of their multiple functions in health and disease. This article discusses the current understanding and controversies on the origin, maintenance and functions of the various populations recognized as T_MP and highlights some potential challenges for deciphering their fate.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466271","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}

{"title":"Human Systems Immunology in the Omics Era: Challenges, Methods, and Emerging Directions","authors":"Lennart Riemann,&nbsp;Reinhold Förster","doi":"10.1002/eji.70164","DOIUrl":"10.1002/eji.70164","url":null,"abstract":"<p>The human immune system is a highly complex, dynamic, and heterogeneous network shaped by genetic, environmental, and temporal influences. Advances in high-throughput omics technologies have transformed our ability to study this complexity directly and comprehensively in human cohorts. These developments have positioned systems immunology as a powerful framework for investigating coordinated immune responses, identifying regulatory mechanisms, and linking molecular patterns to clinical phenotypes. However, the analytical challenges inherent to large-scale, multimodal datasets—including batch effects, small sample sizes, high dimensionality, and substantial interindividual heterogeneity—require rigorous study design, robust statistical modeling, and thoughtful data analysis strategies. In this review, we summarize key technological foundations enabling modern human systems immunology, outline common analytical pitfalls and effective mitigation approaches, discuss data integration concepts, and highlight emerging opportunities in the field. Together, these technological and analytical advances are redefining how immune function is measured and interpreted in real-world human biology and hold significant promise for enhancing mechanistic insight, biomarker discovery, and precision medicine across immunological diseases and interventions.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454926","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}

{"title":"Oleic Acid Promotes Treg Cell Differentiation via Autophagy Induction and Ameliorates DSS-Induced Colitis","authors":"Minghui Xia,&nbsp;Yang Liu,&nbsp;Xiujuan Zhao,&nbsp;Qiuyang Du,&nbsp;Zijie Chen,&nbsp;Jing Wang,&nbsp;Kamran Ghoreschi,&nbsp;Arian Laurence,&nbsp;Xinxin Xiong,&nbsp;Junyan Zhang,&nbsp;Ming Zeng,&nbsp;Xiang-Ping Yang","doi":"10.1002/eji.70173","DOIUrl":"10.1002/eji.70173","url":null,"abstract":"<div>\u0000 \u0000 <p>Oleic acid (OA), a monounsaturated fatty acid (FA) prevalent in olive oil and key component of Mediterranean diet, exhibits anti-inflammatory effects in ulcerative colitis (UC), but its immunomodulatory mechanisms remain largely elusive. Here, we found that OA promotes T regulatory cell (Treg) differentiation in a dose-dependent manner. OA inhibited the activation of the mechanistic target of rapamycin complex 1 (mTORC1) while simultaneously promoting AMP-activated protein kinase (AMPK) activity, both of which are essential for the autophagy pathway. Notably, blockade of autophagy abolished OA-induced Treg differentiation, indicating that autophagy was essential for the immunomodulatory effects of OA. In a dextran sulfate sodium (DSS)-induced colitis model, OA administration significantly increased colonic CD4⁺Foxp3⁺ Treg populations and ameliorated disease severity, including reduced weight loss, bleeding, and histological damage. In summary, our findings revealed that OA promoted Treg differentiation both in vitro and in vivo, suggesting that OA or diets rich in this FA could be promising supplementary therapies for UC.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454910","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}

{"title":"Changes in Adaptive Immunity in Autoimmune Diseases and Aging: Shared Features, Key Differences, and Implications for Immune Vulnerability","authors":"Bojan Jevtić,&nbsp;Milica Lazarević,&nbsp;Đorđe Miljković,&nbsp;Janko Ž. Nikolich","doi":"10.1002/eji.70163","DOIUrl":"10.1002/eji.70163","url":null,"abstract":"<p>Immunologically vulnerable populations (IVP) are particularly at risk of infection due to dysregulated immune responses. Parallels, as well as contrasts, have been drawn between IVP with autoimmune diseases (AI DIS) and older adults, the two by far most numerous IVP, related to their adaptive immune responses. Moreover, beyond the similarities and differences between these two groups, there is accumulating evidence that immune aging can drive certain aspects of autoimmunity. This review integrates existing knowledge regarding the dysregulation of adaptive immune responses in AI DIS and in older adults, while critically examining the similarities, differences, and interrelations between the two in the context of immune responses to infection and vaccination.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429811","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}

{"title":"Heterogeneous Activated B Cell Compartments Arising Early and Transiently After SARS-CoV-2 Vaccination","authors":"Laura Fernandez Blanco,&nbsp;Lisan H. Kuijper,&nbsp;Laura Y.L. Kummer,&nbsp;Niels J.M. Verstegen,&nbsp;Amélie Bos,&nbsp;Mathieu Claireaux,&nbsp;Mariël C. Duurland,&nbsp;Tineke Jorritsma,&nbsp;Maurice Steenhuis,&nbsp;Gius Kerster,&nbsp;Juan J. Garcia Vallejo,&nbsp;Marit J. van Gils,&nbsp;Koos P.J. van Dam,&nbsp;Eileen W. Stalman,&nbsp;Luuk Wieske,&nbsp;Laura Boekel,&nbsp;Gertjan J. Wolbink,&nbsp;Sander W. Tas,&nbsp;Theo Rispens,&nbsp;Taco W. Kuijpers,&nbsp;Filip Eftimov,&nbsp;Anja ten Brinke,&nbsp;S. Marieke van Ham,&nbsp;of T2B! Immunity Against SARS-CoV-2 Study Group","doi":"10.1002/eji.70165","DOIUrl":"10.1002/eji.70165","url":null,"abstract":"<p>In humans, the stages and dynamics of B cell development after antigen encounter remain unclear. Identifying early B cell differentiation stages could reveal biomarkers for humoral immunity and potential targets to prevent unwanted antibody responses. We characterized antigen-specific B cell responses longitudinally after SARS-CoV-2 mRNA vaccination using multiparameter spectral flow cytometry. Spike-specific IgG⁺ CD27⁺ CD71⁺ activated B cells (ActBCs), presumed to be germinal center-derived and IgG⁺ DN2 extrafollicular B cells, dominated the early antigen-specific B cell response, while memory B cells were the main population 6 months after vaccination. Within the IgG⁺ ActBC compartment, we delineated six novel clusters with specific contraction dynamics. Following the second vaccination, certain ActBC clusters displayed sustained expansion over time, being phenotypically similar to memory B cells, while others strongly expanded and subsequently contracted. Several of the rapidly contracting ActBC clusters expressed CD11c, a defining marker for atypical B cells, suggesting a possible extrafollicular origin of these clusters. The transient presence of heterogeneous ActBC clusters was also observed for total B cells when gated in an antigen-independent manner. Characterization of novel ActBC clusters early after antigen encounter helps delineate and dissect the complexity of B cell differentiation, which is vital for understanding unwanted B cell responses.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429744","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}

{"title":"Non-cognate CD8 Binding to MHC I Promotes Positive Selection of an MHC-E Restricted CD8 T Cell Population","authors":"Xiaokun Yang,&nbsp;Melissa A. Colden,&nbsp;Rachel Coombs,&nbsp;Kathya Arana,&nbsp;Dan Tran,&nbsp;Michael Manoharan Valerio,&nbsp;Ellen A. Robey,&nbsp;Laurent Coscoy","doi":"10.1002/eji.70161","DOIUrl":"10.1002/eji.70161","url":null,"abstract":"<p>MHC-E-restricted CD8 T cells are emerging as an attractive therapeutic mechanism due to their strong protective capacity and ability to respond to cells with defects in antigen processing; however, their thymic development remains poorly understood. Here, we explore the MHC ligand requirement for thymic development of T cells reactive to a self-peptide (FL9) presented by mouse MHC-E (Qa1^b) under conditions of deficiency in the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP), called QFL T cells. We show that, while QFL T cells can develop in the absence of the restricting Qa1^b molecule, their development was abrogated in the combined absence of classical MHC Ia and Qa1^b. Interestingly, QFL thymocytes did not recognize classical MHC Ia molecules through their TCR but instead used non-cognate CD8-MHC Ia interactions to boost responses to MHC Ib ligands. Furthermore, we also identify an alternative ligand for the QFL TCR, the MHC Ib molecule H2-T11. Our data provide evidence that both cognate and non-cognate MHC interactions contribute to the development of a Qa1^b-specific T cell population.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429755","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}

{"title":"Viral Immunity in Immunoglobulin Products: Global Immunity Debt and Autoimmunity in the Postpandemic Era","authors":"Hannes Lindahl,&nbsp;Katy Shaw-Saliba,&nbsp;H. Benjamin Larman,&nbsp;C. I. Edvard Smith,&nbsp;Peter Bergman","doi":"10.1002/eji.70162","DOIUrl":"10.1002/eji.70162","url":null,"abstract":"<p>Immunoglobulin (Ig) replacement therapy is commonly used to prevent infections in individuals with low IgG levels. These therapies are derived from pooled plasma donations from thousands of healthy individuals worldwide. This study examined 85 unique Ig batches produced between May 2017 and June 2023 to assess changes in antibody composition, particularly in response to the SARS-CoV-2 pandemic. Using high-throughput assays, IgG reactivity was measured against over 283,000 viral peptides from 527 virus species and nearly 12,000 human proteins. Antibodies against more than 200 virus species were detected, with 27—mainly respiratory and herpesviruses—present in over half the batches. SARS-CoV-2 antibodies emerged in products from July 2021 onward. During the pandemic, antibody levels against influenza, HSV-1, and enterovirus C declined, while those against RSV and Epstein-Barr virus increased. Autoantibodies targeting 55 human proteins were found in multiple batches, with TRIM21/Ro52 antibodies rising in parallel with SARS-CoV-2 antibodies. Principal component analysis showed that neither manufacturer nor geographic origin significantly explained overall antibody profiles, though some manufacturer-specific effects were noted in autoantibody content. These findings highlight pandemic-driven shifts in global antiviral immunity and autoantibody prevalence, with potential implications for immune health and autoimmune disease risk.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429848","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}

{"title":"Single-Cell Profiling of Splenic Immune Ageing and Chronic Stress Adaptations in Mice With Natural Microbiota","authors":"Chinna Susan Philip,&nbsp;Igor Filippov,&nbsp;Uku Haljasorg,&nbsp;Pärt Peterson","doi":"10.1002/eji.70170","DOIUrl":"10.1002/eji.70170","url":null,"abstract":"<p>Immune ageing impairs adaptive and innate responses, yet the spleen remains underexplored by cross-cohort single-cell studies. We profiled splenocytes from young, old and chronically stressed old mice with natural microbiota using single-cell RNA sequencing. Ageing was characterised by reduced lymphocyte competence and elevated stress responses. Within <i>Gzmk</i>⁺ CD8⁺ T cells, young mice were enriched for Gzmk-high cells, whereas in old mice, both Gzmk-high and Gzmk-low cells showed greater heterogeneity and functional alterations: exhaustion in Gzmk-high and inflammation in Gzmk-low cells. Natural killer (NK) cells and macrophages exhibited reduced cytotoxic potential and sustained pro-inflammatory polarisation, respectively. Chronic stress caused modest compositional shifts that partially counteracted age-related changes. Furthermore, we integrated our dataset with six published datasets to build a comprehensive atlas with &gt; 272,000 splenocytes. Atlas-level annotation showed reproducible compositional shifts across datasets. Conserved ageing signatures included loss of NK effector genes (<i>Zeb2, Prf1</i>), decline of naïve T quiescence (<i>Lef1, Il7r</i>) with stress induction (<i>Rbm3, Socs3</i>), gain of survival/pro-inflammatory/exhaustion genes (<i>Bcl2, S100a6, Ccl5, Lag3</i>) in effector T cells, and altered differentiation and regulation (<i>Zbtb32, Zbtb20, Zfp318, Ighd, Cr2</i>) in B cells. Our results define conserved features of splenic immunosenescence and provide an atlas for dissecting splenic immune alterations.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429794","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}

{"title":"Transcriptome–Proteome Analysis of Human Naive and Memory B Cell Subsets Reveals Isotype and Subclass-Specific Phenotypes","authors":"Jana Koers,&nbsp;Arie J. Hoogendijk,&nbsp;Simon Tol,&nbsp;Floris P.J. Van Alphen,&nbsp;Ninotska I.L. Derksen,&nbsp;Maartje van den Biggelaar,&nbsp;Theo Rispens","doi":"10.1002/eji.70159","DOIUrl":"10.1002/eji.70159","url":null,"abstract":"<p>Antibodies produced by B cells aid in the recognition and clearance of pathogens and are the cornerstone of vaccination strategies. Humans produce nine different antibody isotypes, and their effector functions differ according to the type of antigen and route of exposure. Phenotypic variation between isotype-switched B cell subsets is expected but not studied in detail. To obtain a molecular definition of isotype-defined cell identity, we performed proteomics and transcriptomics on isotype-defined populations of human naive and memory B cells (MBCs): CD27⁻IgM⁺IgD⁺, CD27⁺CD38^lo/−IgM⁺IgD⁺, CD27⁺CD38^lo/−IgM⁺IgD⁻, and IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4 MBCs (CD27⁺CD38^lo/−Ig⁺). Combined proteome and transcriptome analysis revealed that mRNA and protein expression profiles separate isotype-defined B cell subsets according to their differentiation status. mRNA and protein expression levels correlated reasonably well for many genes. IgG4-switched B cells were most distinct from naive B cells in terms of mRNA as well as protein expression profiles. Besides a distinct expression profile of cytokine and Fc receptors, we identified a high expression of IgE-coding mRNA in IgG4-switched B cells. SDR16C5 was identified as uniquely upregulated in IgG4-switched B cells. Taken together, this study highlights the distinct phenotypic profile of IgG4-switched B cells.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429887","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}