European Journal of Immunology最新文献

{"title":"Emerging Voices in Immunology: Local Environments, Molecular Controls and the Line Between Protection and Pathology","authors":"Myriam Nabhan, Annika Hausmann, Ioana Sandu, Melissa van Gool, Jill de Mol","doi":"10.1002/eji.70314","DOIUrl":"10.1002/eji.70314","url":null,"abstract":"<p></p><p>Image designed by yEFIS member Ines Poljak.</p><p>In 2024, immunologists from around the world met in Dublin for the seventh European Congress of Immunology (ECI). The Young Immunologist Network of the European Federation of Immunological Societies (yEFIS) partnered with EJI to highlight the work of ECRs, including 16 Bright Sparks Winners presenting their work during the congress. Resulting from this initiative, we present 23 articles led by young researchers from 16 countries across Europe, Asia, and the USA, including research articles and reviews covering a variety of topics in basic, translational, and clinical immunology. Among these, a recent study led by Shimon Sakaguchi, 2025 Nobel laureate in Physiology or Medicine, sheds light into the mechanism of Treg-mediated immune homeostasis in the colon. This collaboration resulted in the present special issue showcasing the diversity, both scientific and geographical, of the immunological community. “Emerging voices in immunology: local environments, molecular controls and the line between protection and pathology” covers novel insights on a broad spectrum of topics, from tissue immunity, immune mechanisms, and cell signaling to antiviral immunity, tolerance, and autoimmunity.</p><p>In the past decades, immunity in systemic lymphoid organs has been a major focus of immunological research. This research has uncovered important fundamental and translational insights especially into regulation of adaptive immune responses. It becomes more and more evident, however, that immunity at different body sites is highly adapted to the local needs and circumstances. These can differ quite drastically, and several articles in this issue highlight this diversity.</p><p>Lorga and Bonifácio Andrade review the unique role of the meningeal immune system, which, despite constituting the barrier to the immunoprivileged central nervous system, harbors an immense immune cell repertoire, which plays a central role in steady state maintenance as well as pathological conditions [<span>1</span>].</p><p>In stark contrast to the shielded CNS, the gastrointestinal immune system is constantly exposed to a huge variety of external stimuli. This poses a strong risk for the development of intestinal inflammation, such as in inflammatory bowel disease. Crohn's disease, a subform of inflammatory bowel disease, is associated with creeping fat development, a site of immune activation and pro-fibrotic reprogramming. Omar et al. provide an overview on the current knowledge and model systems to gain further insights into pathogenesis of this inflammatory disease [<span>2</span>]. Similarly, O'Neill et al. highlight how pathological niches like the tumor environment can modulate tissue immunity via modulation of surface molecule glycosylation to promote pathology [<span>3</span>].</p><p>Synovial immune cells, on the other hand, have to withstand mechanical stress and comprise a much higher diversity than previously anticipat","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331847","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":"Antigen-Experience Imprints Integrin Expression in Human B Cells","authors":"Bianca Laura Cinicola,&nbsp;Mattia Laffranchi,&nbsp;Chiara Sugoni,&nbsp;Gabriele Volpe,&nbsp;Christian Albano,&nbsp;Federica Pulvirenti,&nbsp;Salvatore Zaffina,&nbsp;Maria Rosaria Vinci,&nbsp;Reparata Rosa Di Prinzio,&nbsp;Anna Maria Zicari,&nbsp;Isabella Quinti,&nbsp;Silvano Sozzani,&nbsp;Rita Carsetti,&nbsp;Eva Piano Mortari","doi":"10.1002/eji.70316","DOIUrl":"10.1002/eji.70316","url":null,"abstract":"<div>\u0000 \u0000 <p>Integrins are critical regulators of lymphocyte adhesion and migration, shaping immune responses by directing cells to specific tissues. In B cells, integrin expression is dynamically regulated during differentiation and activation, yet it is incompletely understood whether immunization and infection influence these pathways. Here, we investigated the expression and regulation of the α4β1 and α4β7 integrins across circulating human B-cell subsets in adults and children following SARS-CoV-2 vaccination and/or infection. By combining flow cytometry, bulk and paired single-cell RNA and VDJ sequencing, and antigen-specific analyses, we show that naïve and early memory B cells predominantly express β7, while antigen experience drives the emergence of two integrin-imprinted memory lineages characterized by β7 or β1 expression. The highest integrin levels were observed in activated memory B cells (actMBCs) and plasmablasts, indicating enhanced migratory potential. Integrin expression was linked both to the maturation stage and to the immunoglobulin isotype. Importantly, SARS-CoV-2 infection—either before or after vaccination—significantly increased the frequency of β1-expressing memory B cells in both adults and children, particularly among spike-specific actMBCs. Single-cell analyses further identified distinct actMBC subsets with divergent integrin profiles and activation dynamics. Together, our findings demonstrate that respiratory viral infection imprints durable migratory programs on antigen-specific B cells, favoring α4β1 expression, with implications for tissue targeting and the design of next-generation mucosal vaccines.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316435","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":"Immune Regulation by Regnase-1 and Related Endoribonucleases","authors":"Takuya Uehata,&nbsp;Osamu Takeuchi","doi":"10.1002/eji.70313","DOIUrl":"10.1002/eji.70313","url":null,"abstract":"<p>Regnase-1 (ZC3H12A) is a stem-loop (SL)-recognizing endoribonuclease that couples immune stimulation to selective mRNA decay. Although originally characterized as a negative regulator of inflammatory cytokine expression, recent studies have expanded this view by placing Regnase-1 within a broader network of SL-recognizing RNA decay factors, including Roquin proteins and Regnase-3, and by revealing context-dependent functions in immune and nonimmune cells. Through regulation of transcripts encoding cytokines, costimulatory molecules, and transcriptional regulators, Regnase-1 restrains innate and adaptive immune activation, but biological output varies according to cell type, tissue environment, disease stage, and mode of perturbation. In T cells, including engineered T cells used in adoptive cell therapy, Regnase-1 inhibition can enhance antitumor activity in preclinical models, whereas in epithelial tissues Regnase-1 can limit inflammatory circuits that affect host defense, tissue injury, and inflammation-associated tumorigenesis. Structure-targeting antisense oligonucleotides and genome-editing approaches have further raised the possibility of therapeutically modulating Regnase-dependent RNA decay. In this Review, we discuss molecular mechanisms of Regnase-1-mediated mRNA decay, context-dependent functions across tissues and diseases, and the opportunities and limitations of targeting this pathway therapeutically.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13732794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316436","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":"Cover Story: Eur. J. Immunol. 11'26","authors":"","doi":"10.1002/eji.70318","DOIUrl":"https://doi.org/10.1002/eji.70318","url":null,"abstract":"<p>Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312644","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":"High Expression of ACKR4 in Thymic Epithelial Progenitors of Adult Mice","authors":"Elin Hub,&nbsp;Chikako Odaka,&nbsp;Stefan Russo,&nbsp;Christina Gkantsinikoudi,&nbsp;Maryna Samus,&nbsp;Neil Dufton,&nbsp;Shigeo Murata,&nbsp;Antal Rot","doi":"10.1002/eji.70305","DOIUrl":"10.1002/eji.70305","url":null,"abstract":"<p>High ACKR4-expressing cells located in the subcapsular zone and around pericytes at the corticomedullary junction express thymic epithelial cell (TEC) progenitor markers. During cortical TEC regeneration in adult mice, ACKR4 expression is upregulated in cells expressing the transcription factors p63 and Foxn1. Our findings suggest that ACKR4 is preferentially expressed in thymic epithelial progenitors in adult mice.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293526","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":"Issue Information: Eur. J. Immunol. 11'26","authors":"","doi":"10.1002/eji.70317","DOIUrl":"https://doi.org/10.1002/eji.70317","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312645","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":"Increased Output of Recent Thymic Emigrants Contributes to Reconstitution of T-Cell Pool During Recovery From COVID-19","authors":"Xiaobo Huang,&nbsp;Suvi T. Jokiranta,&nbsp;Kirsten Nowlan,&nbsp;Ngoc Anh Nguyen,&nbsp;Nelli Heikkilä,&nbsp;Lauriina Tola,&nbsp;Anu Kantele,&nbsp;Pirkka T. Pekkarinen,&nbsp;Johanna Hästbacka,&nbsp;Olli Vapalahti,&nbsp;Santtu Heinonen,&nbsp;Juuso Paajanen,&nbsp;Tomas Strandin,&nbsp;Eliisa Kekäläinen","doi":"10.1002/eji.70303","DOIUrl":"10.1002/eji.70303","url":null,"abstract":"<p>Acute coronavirus disease 2019 (COVID-19) causes marked T-cell lymphopenia, with recovery potentially driven by peripheral proliferation or increased thymic output of recent thymic emigrants (RTEs). We examined the relative contribution of these mechanisms by analyzing naïve T-cell and RTE dynamics in 63 patients sampled at 1–3 timepoints during and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Overall frequencies of naïve CD4+ and CD8+ T cells remained stable during convalescence. In a female-biased subcohort with paired samples, CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset frequencies increased from acute to late convalescence (LC) stage. Across the full cohort, a significant increase was confirmed for CD21+ CD8+ RTE-enriched subsets. PD-1 and Ki67 expression did not explain this rise, indicating enhancement of thymic output despite the cohort's high median age. Patients requiring ICU care had lower CD31+ CD4+ RTE-enriched subset frequencies in LC compared with non-ICU cases. Regression coefficient modeling identified male sex as a negative predictor of CD31+ CD4+ RTE-enriched subset frequency, potentially contributing to distinct CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset kinetics. Together, these findings suggest that de novo thymic output, particularly CD21+ CD8+ RTE-enriched subset, contributes to T-cell reconstitution after COVID-19 and may influence susceptibility to post-infectious immune dysregulation.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293498","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":"MICA Allelic Variation Modulates Secretion and Protein Flexibility, Impacting on NKG2D-Mediated Immune Responses and Antibody Detection","authors":"Silvia López-Borrego,&nbsp;Karen Toledo-Stuardo,&nbsp;Douglas J. Matthies,&nbsp;Marta González-Matesanz,&nbsp;María Carmen Molina,&nbsp;Mar Valés-Gómez","doi":"10.1002/eji.70304","DOIUrl":"10.1002/eji.70304","url":null,"abstract":"<p>NKG2D is an essential receptor for cancer immunosurveillance, activating Natural Killer (NK) and CD8⁺ T-cells to eliminate transformed cells. However, release of its ligands promotes immune evasion. Although new therapeutic strategies aim to block NKG2D-ligand shedding, the impact of allelic polymorphism on secretion mechanisms, either as soluble proteins or within extracellular vesicles (EVs), remains insufficiently explored. The glycosyl–phosphatidyl–inositol (GPI)-anchored MICA (MHC class I chain-related gene A) *008 allele is preferentially incorporated into EVs, but little is known about the EV release of other alleles. Here, we compared five MICA alleles and found that non-GPI-MICA can also be incorporated into EVs through a palmitoylation-dependent process, although with much lower efficiency compared with GPI-anchored alleles, such as MICA*008. EVs containing MICA decreased NKG2D detection and impaired NK cell function, whereas soluble MICA had negligible effects. The strength of these effects was related to MICA allele identity. In addition to affinity (ruled by dimorphism at position 129), predictions of differences in MICA structural dynamics and NKG2D binding energetics coincided with the differential capacity of alleles to modulate NKG2D and to bind certain anti-MICA antibodies. Given the clinical potential of MICA as a biomarker and therapeutic target, defining the biology and immune impact of allelic variants is essential to optimize strategies aimed at restoring NKG2D-dependent antitumor immunity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13714556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284268","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":"Broken Engines of Immunity: Mitochondrial Dysfunction in T Cells Across Cancer and Complex Pathologies","authors":"Carolina Brescia,&nbsp;Giuseppe Viglietto,&nbsp;Rosario Amato","doi":"10.1002/eji.70300","DOIUrl":"10.1002/eji.70300","url":null,"abstract":"<p>Mitochondria have traditionally been viewed as the cellular ‘powerhouses’ responsible for energy production; however, they also play essential roles in a wide range of cellular processes, including macromolecule biosynthesis and the regulation of apoptosis. Accumulating evidence highlights their importance in immune regulation, particularly through their influence on T cell activation, proliferation, and effector function. In addition to ATP generation, mitochondria regulate redox and calcium homeostasis and produce metabolites that modulate the transcriptional and epigenetic programs of immune cells. Upon antigen recognition, T lymphocytes undergo marked metabolic reprogramming, characterised by increased glycolysis while preserving mitochondrial metabolism as a critical pathway. Mitochondrial dysfunction disrupts intracellular signalling and contributes to T cell exhaustion in diverse pathological contexts, including cancer and chronic viral infections. Consequently, strategies aimed at restoring mitochondrial function are emerging as promising therapeutic approaches to correct immune dysfunction driven by impaired T cell responses. Importantly, these alterations should not be interpreted solely as downstream consequences of chronic immune stimulation; rather, mitochondrial dysfunction can actively determine T-cell fate, stabilise exhaustion-associated programs, and define the extent to which dysfunctional T cells remain therapeutically reversible. This review first outlines mitochondrial structure, bioenergetics, dynamics, and quality-control pathways and then examines how these processes are remodelled across naïve, effector, circulating-memory, tissue-resident-memory, and exhausted T-cell states. It subsequently integrates evidence from cancer, chronic viral infection, and ageing and evaluates mitochondria-directed strategies for restoring T-cell function.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13714555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284311","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":"Prophylactic Soraphen A Treatment Attenuates Western Diet-Exacerbated IMQ-Induced Psoriasiform Inflammation","authors":"Yu-San Kao,&nbsp;Katharina S. Kommoss,&nbsp;Tabea Bieler,&nbsp;Gloria Janet Godoy,&nbsp;Aleksandra Lopez Krol,&nbsp;Fatima Boukhallouk,&nbsp;Felix K. F. Kommoss,&nbsp;Danijela Heide,&nbsp;Susanne H. Kirsch,&nbsp;Rolf Müller,&nbsp;Mathias Heikenwälder,&nbsp;Tim Sparwasser","doi":"10.1002/eji.70298","DOIUrl":"10.1002/eji.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Psoriasis is a T-cell-mediated inflammatory disease amplified by metabolic stress. Acetyl-CoA carboxylase 1 (ACC1)-dependent fatty acid synthesis is required for IL-17-producing T cells. Here, we asked whether short-term systemic administration of soraphen A (SorA), a dual ACC1/2 inhibitor, modulates imiquimod (IMQ)-induced psoriasiform inflammation under normal diet (ND) and Western diet (WD) conditions. Female C57BL/6J mice were fed ND or WD for 12 weeks prior to daily intraperitoneal injections of SorA or vehicle for 10 days, followed by 5 days of topical IMQ to induce psoriasiform dermatitis. Disease severity was assessed by macroscopic, histological, transcriptional, and flow cytometric readouts. Prophylactic SorA administration had no measurable effect in ND-fed mice. In WD-fed mice, prophylactic SorA reduced erythema, back skin thickening, and epidermal hyperplasia, whereas scaling remained unchanged. Selected histological skin readouts were numerically lower, whereas the qPCR panel showed no statistically significant differences. In skin-draining lymph nodes, IL-17A⁺ CD4⁺ and CD8⁺ T-cell frequencies and numbers were significantly reduced, whereas γδT17 cells did not differ significantly. Hepatic steatosis scores were unchanged, but hepatic neutrophil infiltration was reduced. Under the present prophylactic regimen, systemic SorA administration was associated with modest attenuation of WD-exacerbated IMQ-induced psoriasiform inflammation. These findings support further preclinical evaluation of ACC-targeted immunometabolic interventions in metabolically aggravated psoriasiform inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13714554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284287","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}