European Journal of Immunology最新文献

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55th Annual Meeting of the German Society for Immunology (DGfI), 15–18 September, 2026, Munich, Germany 第55届德国免疫学学会年会(DGfI), 2026年9月15-18日,德国慕尼黑
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-09-04 DOI: 10.1002/eji.70263
{"title":"55th Annual Meeting of the German Society for Immunology (DGfI), 15–18 September, 2026, Munich, Germany","authors":"","doi":"10.1002/eji.70263","DOIUrl":"https://doi.org/10.1002/eji.70263","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 S4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878238","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
Cellular and Humoral Immune Responses to Noncanonical Enterotoxigenic Escherichia coli Virulence Factors. 对非典型产肠毒素大肠杆菌毒力因子的细胞和体液免疫反应。
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-09-01 DOI: 10.1002/eji.70246
Saman Riaz, Sehee Rim, Hans Steinsland, Oda Barth Vedøy, Tim J Vickers, James M Fleckenstein, Kurt Hanevik
{"title":"Cellular and Humoral Immune Responses to Noncanonical Enterotoxigenic Escherichia coli Virulence Factors.","authors":"Saman Riaz, Sehee Rim, Hans Steinsland, Oda Barth Vedøy, Tim J Vickers, James M Fleckenstein, Kurt Hanevik","doi":"10.1002/eji.70246","DOIUrl":"10.1002/eji.70246","url":null,"abstract":"<p><p>A broadly protective licensed vaccine against enterotoxigenic Escherichia coli (ETEC) remains unavailable. To inform rational ETEC vaccine design, we characterized immune responses to the noncanonical antigens EatA mucinase, EtpA adhesin, and YghJ metalloprotease following experimental ETEC infection. We analyzed longitudinal cellular and humoral responses to EatA, EtpA, and YghJ in 30 volunteers infected with ETEC. Antigen-specific CD4<sup>+</sup> T cell responses were assessed using an activation-induced marker (AIM) assay detecting CD69, CD134, CD137, and CD154 expression after antigen stimulation. Antigen-specific IgA and IgG responses in serum and IgA responses in intestinal lavage were quantified using bead-based multiplex flow cytometry. Antigen-reactive CD69<sup>+</sup>CD134<sup>+</sup> CD4<sup>+</sup> T cells increased on Day 10 for all three antigens, with EtpA also inducing CD134<sup>+</sup>CD137<sup>+</sup> responses. Serum anti-EatA IgA and IgG increased on Days 10 and 28, accompanied by increased intestinal lavage anti-EatA IgA on Day 10. Mucosal IgA responses to EatA and EtpA correlated strongly with systemic IgG. Immune responses did not seem to be associated with ETEC colonization or host blood group. This first integrated characterization of human immune responses against the ETEC antigens EatA, EtpA, and YghJ demonstrates their immunogenicity in both cellular and humoral compartments, and supports their relevance as potential vaccine targets.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 9","pages":"e70246"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872395","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
Isoform-Level Analysis Reveals Reproducible Early Changes in Transcript Usage During Human Vaccine Responses 异构体水平分析揭示了人类疫苗应答过程中转录物使用可重复的早期变化
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-30 DOI: 10.1002/eji.70277
Lennart Riemann, Ahmed Hassan, Swantje Hammerschmidt, Anja Schimrock, Gunnar Schmidt, Nataliya Di Donato, Reinhold Förster
{"title":"Isoform-Level Analysis Reveals Reproducible Early Changes in Transcript Usage During Human Vaccine Responses","authors":"Lennart Riemann,&nbsp;Ahmed Hassan,&nbsp;Swantje Hammerschmidt,&nbsp;Anja Schimrock,&nbsp;Gunnar Schmidt,&nbsp;Nataliya Di Donato,&nbsp;Reinhold Förster","doi":"10.1002/eji.70277","DOIUrl":"https://doi.org/10.1002/eji.70277","url":null,"abstract":"<p>Vaccine-induced transcriptional responses have been extensively characterized at the gene level, but whether vaccination also alters transcript isoform usage remains largely unexplored. Here, we reanalyzed longitudinal whole-blood RNA-seq data from a discovery cohort of mRNA COVID-19 vaccine recipients using the IsoformSwitchAnalyzeR framework and validated the findings in an independent cohort. Key findings were validated by full-length RNA long-read sequencing and extended to four additional vaccine cohorts covering distinct platforms and pathogens. mRNA vaccination induced a rapid and transient wave of differential transcript usage, peaking at 24 h post-vaccination with 131 isoforms significantly altered across 107 genes, before largely resolving by Day 14. Isoform switching events were reproducible across independent cohorts and confirmed by full-length RNA long-read sequencing. Structural annotation of switching transcripts, including <i>RMI2</i>, <i>WARS1</i>, and <i>NT5C3A</i>, revealed changes affecting predicted protein domains and signal peptides. Notably, highly concordant isoform switching patterns were observed across MVA-based SARS-CoV-2, influenza, and Ebola vaccine cohorts and showed dose-dependent modulation. Overall, differential transcript isoform usage is a rapid and transient feature of the early human immune response to vaccination that was observed across multiple vaccine platforms. These findings reveal an underappreciated layer of transcriptional regulation that complements conventional gene-level analyses and warrants integration into future vaccine immunogenicity studies.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860201","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
Cover Story: Eur. J. Immunol. 9'26 封面故事:欧元。[j] .免疫学杂志。9'26
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-30 DOI: 10.1002/eji.70281
{"title":"Cover Story: Eur. J. Immunol. 9'26","authors":"","doi":"10.1002/eji.70281","DOIUrl":"https://doi.org/10.1002/eji.70281","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 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860199","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
Issue Information: Eur. J. Immunol. 9'26 发行信息:欧元。[j] .免疫学杂志。9'26
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-30 DOI: 10.1002/eji.70280
{"title":"Issue Information: Eur. J. Immunol. 9'26","authors":"","doi":"10.1002/eji.70280","DOIUrl":"https://doi.org/10.1002/eji.70280","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860200","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
Serological Predictors of Protection from Infection Upon Household Exposure to SARS-CoV-2 家庭暴露于SARS-CoV-2后预防感染的血清学预测因子
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-24 DOI: 10.1002/eji.70269
Henrike Maaß, Imke Hinrichs, Martina Pavletic, Manuela Harries, Tatjana Prinke, Najat Bdeir, Richard Egelkamp, Berit Lange, Yannic C. Bartsch, Mate Lerga, Luka Cicin-Sain
{"title":"Serological Predictors of Protection from Infection Upon Household Exposure to SARS-CoV-2","authors":"Henrike Maaß,&nbsp;Imke Hinrichs,&nbsp;Martina Pavletic,&nbsp;Manuela Harries,&nbsp;Tatjana Prinke,&nbsp;Najat Bdeir,&nbsp;Richard Egelkamp,&nbsp;Berit Lange,&nbsp;Yannic C. Bartsch,&nbsp;Mate Lerga,&nbsp;Luka Cicin-Sain","doi":"10.1002/eji.70269","DOIUrl":"10.1002/eji.70269","url":null,"abstract":"<p>Correlates of protection against symptomatic and severe breakthrough SARS-CoV-2 infections are well characterized. However, correlates of protection against virus transmission are poorly defined due to a lack of evidence in well-designed prospective clinical trials. We studied a Croatian cohort of individuals with documented household exposure to SARS-CoV-2 in late 2022/early 2023. Sera were acquired at the time of the COVID-19 diagnosis of the index case and before symptom onset of the test case. Samples were comprehensively analyzed for predictors of protection against virus transmission. PCR-negative participants at day 0 were recalled 14 days later and re-tested by PCR and IgM ELISA to identify any virus transmission, including asymptomatic ones. Out of nearly 200 tested serological parameters, several serological features differed between the participants that became PCR-positive during the study period and those that remained PCR-negative, although none remained significant after correction for multiple testing in the full cohort. Titers of variant-specific neutralizing antibody showed the biggest difference and were higher in the uninfected subgroup. Since recent antigenic exposure may confound results, we identified the recipients exhibiting IgM seroconversion and censored them from the study. This refinement clearly separated infected and uninfected individuals by variant-specific neutralization titers and IgA1 responses to BA4/5 RBD, which remained significant after correction. Therefore, our data indicate that high IgA1 and neutralizing titers may be predictive serum correlates of protection against SARS-CoV-2 transmission in intense contacts among household members, but only if variant-specific antigen is used in serological assays.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807933","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
A Bacterial Microbiome Is Dispensable for the Induction of CD8 T Cell Exhaustion 细菌微生物组对于诱导CD8 T细胞衰竭是必不可少的。
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-24 DOI: 10.1002/eji.70238
Miriam Kuhlmann, Daphne Del Carmen Kolland, Gustavo Pereira de Almeida, Christian Hoffmann, Madlaina von Hoesslin, Jacqueline Berner, Christine Wurmser, Anna Akulich, Anna M. Schulz, Carl-Philipp Hackstein, Caspar Ohnmacht, Dietmar Zehn
{"title":"A Bacterial Microbiome Is Dispensable for the Induction of CD8 T Cell Exhaustion","authors":"Miriam Kuhlmann,&nbsp;Daphne Del Carmen Kolland,&nbsp;Gustavo Pereira de Almeida,&nbsp;Christian Hoffmann,&nbsp;Madlaina von Hoesslin,&nbsp;Jacqueline Berner,&nbsp;Christine Wurmser,&nbsp;Anna Akulich,&nbsp;Anna M. Schulz,&nbsp;Carl-Philipp Hackstein,&nbsp;Caspar Ohnmacht,&nbsp;Dietmar Zehn","doi":"10.1002/eji.70238","DOIUrl":"10.1002/eji.70238","url":null,"abstract":"<p>Prolonged antigen exposure in chronic viral infections reduces the effector capacity of cytotoxic T cells—a phenomenon known as T cell exhaustion. Development of T cell exhaustion is driven by high viral titers, strong TCR stimulation, and high antigen concentrations associated with strong inflammatory signals. A largely unexplored factor has been the influence of the microbiome in these processes. Here, we report that T cell exhaustion progresses independently of the presence or absence of a microbiome in chronic lymphocytic choriomeningitis virus (LCMV) infections. Virus-specific CD8 T cells in germ-free mice showed high expression of the inhibitory receptor PD-1 and decreased cytokine production. Moreover, their global gene expression patterns, as determined by single-cell sequencing, were similar to those of cells in specific pathogen-free mice. In line with this, we observed similar pathogen loads with and without a microbiome. Thus, our study demonstrates that the microbiome is dispensable for the induction of T cell exhaustion and for the limited virus control seen in chronic LCMV infections.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807988","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
IL-9 Is Essential for ILC2-Mediated but Not Th2- and Th17-Cell-Mediated Allergic Airway Inflammation in Mice IL-9对ilc2介导的小鼠变应性气道炎症至关重要,而不是Th2和th17细胞介导的气道炎症。
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-24 DOI: 10.1002/eji.70270
Nikolaos D. Sidiropoulos, Franziska Ampenberger, Christoph Schlapbach, Christoph Schneider, Manfred Kopf
{"title":"IL-9 Is Essential for ILC2-Mediated but Not Th2- and Th17-Cell-Mediated Allergic Airway Inflammation in Mice","authors":"Nikolaos D. Sidiropoulos,&nbsp;Franziska Ampenberger,&nbsp;Christoph Schlapbach,&nbsp;Christoph Schneider,&nbsp;Manfred Kopf","doi":"10.1002/eji.70270","DOIUrl":"10.1002/eji.70270","url":null,"abstract":"<p>Interleukin-9 (IL-9) has primarily been associated with type 2 immunity in health and disease. While its impact on innate lymphoid cells (ILC2s) is well known, the cellular targets and mechanisms underlying type 2 immunity remain incompletely understood. In this study, we report the generation of a mouse-specific anti-IL-9 receptor (IL-9R) antibody, enabling us to accurately map IL-9R protein expression across various immune cell types. In naïve mice, IL-9R was detectable in ILC2s, marginal zone B cells, and B1b cells. In allergic lung inflammation, a subset of CD4<sup>+</sup> T cells faintly upregulated IL-9R, whereas DCs, macrophages, eosinophils, and neutrophils remained IL-9R-negative. Functionally, IL-9R was found to significantly contribute to ILC2 expansion, their effector cytokine production, and eosinophilia in the papain asthma model. However, in the context of acute and chronic HDM exposure, IL-9R was dispensable for both allergic lung inflammation and CD4-dependent memory-type 2 responses. Using mixed bone marrow chimeras in which IL-9R is selectively absent in T cells, we confirmed that IL-9R signaling in T cells does not critically impact chronic Th2 and Th17 responses. Lastly, using mice selectively lacking ILC2s, we demonstrate that this population is the culprit of pathological type 2 immunity in the lung in both papain- and acute HDM-induced asthma models. Together, our results establish that IL-9 is a critical regulator of ILC2-dependent type 2 immunity, while its effects on T cell-dependent responses are minimal. These findings provide a foundation for future studies exploring the therapeutic modulation of IL-9 signaling in allergy and other inflammatory diseases.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807993","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
Single-Cell Profiling Identifies Skin-Resident Memory CD4+ T Cells as a Potential Correlate of Immunity During Staphylococcus aureus Skin Infection 单细胞分析鉴定皮肤常驻记忆CD4+ T细胞作为金黄色葡萄球菌皮肤感染期间免疫的潜在相关
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-24 DOI: 10.1002/eji.70268
Jonah Clegg, Giovanni Cova, Alberto Carignano, Megan Smith, Emiliano Chiarot, Simona Tavarini, Chiara Sammicheli, Nicholas Rachmaninoff, Serena Vastola, Silvia Guidotti, Emilio Siena, Monia Bardelli, Fabio Bagnoli, Michela Brazzoli, Rachel M. McLoughlin, Elisabetta Soldaini
{"title":"Single-Cell Profiling Identifies Skin-Resident Memory CD4+ T Cells as a Potential Correlate of Immunity During Staphylococcus aureus Skin Infection","authors":"Jonah Clegg,&nbsp;Giovanni Cova,&nbsp;Alberto Carignano,&nbsp;Megan Smith,&nbsp;Emiliano Chiarot,&nbsp;Simona Tavarini,&nbsp;Chiara Sammicheli,&nbsp;Nicholas Rachmaninoff,&nbsp;Serena Vastola,&nbsp;Silvia Guidotti,&nbsp;Emilio Siena,&nbsp;Monia Bardelli,&nbsp;Fabio Bagnoli,&nbsp;Michela Brazzoli,&nbsp;Rachel M. McLoughlin,&nbsp;Elisabetta Soldaini","doi":"10.1002/eji.70268","DOIUrl":"10.1002/eji.70268","url":null,"abstract":"<p><i>Staphylococcus aureus</i> is a leading cause of skin and soft tissue infections (SSTIs), yet the cellular mediators of protective memory remain incompletely defined. Using a self-resolving murine SSTI model, we combined longitudinal single-cell RNA sequencing with flow cytometry to characterize immune memory within the skin following infection. We identified a persistent population of CD4<sup>+</sup> T cells that remained in the skin after bacterial clearance and acquired a transcriptional program consistent with tissue residency, including expression of genes associated with tissue retention and long-term residence. Phenotypic analysis confirmed the emergence of a skin-resident memory T cell (Trm) population that persisted well beyond resolution of infection and displayed characteristics of a clonal T cell response. Upon reinfection, protective immunity was associated with rapid recall responses from these resident cells and was maintained despite FTY720-mediated blockade of lymphocyte egress from secondary lymphoid organs, demonstrating that circulating lymphocytes were dispensable for protection. Together, these findings identify infection-induced CD4<sup>+</sup> Trms as a durable component of immune memory following <i>S. aureus</i> SSTI and support a role for tissue-resident immunity in protection against recurrent infection, highlighting CD4<sup>+</sup> Trms as a potential target for future vaccine strategies.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808010","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
The Glucose Transporter GLUT3 Controls Regulatory T Cell Function 葡萄糖转运体GLUT3控制调节性T细胞功能。
IF 4.1 3区 医学
European Journal of Immunology Pub Date : 2026-08-24 DOI: 10.1002/eji.70272
Katrin Sinning, Miriam Eckstein, Xiufeng Zhao, Alexandra Freitag, Mathias Rosenfeldt, Sophia M. Hochrein, Martin Vaeth
{"title":"The Glucose Transporter GLUT3 Controls Regulatory T Cell Function","authors":"Katrin Sinning,&nbsp;Miriam Eckstein,&nbsp;Xiufeng Zhao,&nbsp;Alexandra Freitag,&nbsp;Mathias Rosenfeldt,&nbsp;Sophia M. Hochrein,&nbsp;Martin Vaeth","doi":"10.1002/eji.70272","DOIUrl":"10.1002/eji.70272","url":null,"abstract":"<p>Regulatory T (Treg) cells are central mediators of immune tolerance and are generally considered to rely predominantly on mitochondrial metabolism rather than glucose-driven glycolysis. To define the role of glucose metabolism in Treg cells, we investigated the contribution of the hexose transporters GLUT1 and GLUT3. Genetic ablation of GLUT1 in T cells or selectively in Treg cells had minimal impact on Treg cell numbers, phenotype, or immune homeostasis, indicating that GLUT1 is largely dispensable in this lineage. By contrast, deletion of GLUT3 in T cells resulted in a marked reduction in Treg cell numbers. However, it remained unclear whether this reduction reflected diminished IL-2 production by GLUT3-deficient conventional T cells or a cell-intrinsic requirement for GLUT3 in Treg cells. To investigate this, we generated mice with Treg cell-specific deletion of GLUT3. These animals developed severe systemic inflammation accompanied by lethal cellular and humoral autoimmunity. Mechanistically, GLUT3-deficient Treg cells exhibited reduced glycolytic activity and mitochondrial respiration, leading to impaired suppressive function and defective effector and follicular Treg cell differentiation. Collectively, our findings demonstrate a nonredundant requirement for GLUT3 in Treg cell metabolic fitness and immune regulation, refining the prevailing view that Treg cells operate largely independently of glucose metabolism. Our data further suggest that therapeutic strategies targeting glucose uptake and glycolysis in autoimmune and inflammatory diseases should account for potential adverse effects on Treg cell-mediated immune tolerance.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808049","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
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