European Journal of Immunology最新文献_第10页

Beyond FoxP3—Identification of a Chicken Regulatory T Cell Signature 超越foxp3 -鸡调节性T细胞特征的鉴定

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70106

Isabell Naumann, Edward S. Ricemeyer, Daniel Elleder, Jiri Plachy, Dominik von La Roche, Kim Vučinić, Thomas W. Göbel, Bernd Kaspers, Simon P. Früh, Sonja Härtle

{"title":"Beyond FoxP3—Identification of a Chicken Regulatory T Cell Signature","authors":"Isabell Naumann, Edward S. Ricemeyer, Daniel Elleder, Jiri Plachy, Dominik von La Roche, Kim Vučinić, Thomas W. Göbel, Bernd Kaspers, Simon P. Früh, Sonja Härtle","doi":"10.1002/eji.70106","DOIUrl":"10.1002/eji.70106","url":null,"abstract":"Regulatory T cells (Tregs), defined by the lineage-specific transcription factor FoxP3, are crucial for immune regulation and have been studied extensively in mammals. However, avian Tregs remain poorly characterized, leaving gaps in our understanding of their evolutionary conservation and unique features. In this study, we investigated the phenotype of chicken Tregs to define reliable markers for their identification and characterization. We analyzed CD4+ splenocytes sorted into CD25negative, CD25low, and CD25high subpopulations using RNA sequencing. FOXP3 and other Treg-associated genes were expressed in both CD25low and CD25high populations, showing that CD25 expression alone is insufficient to distinguish chicken Tregs. To refine the marker profile, we evaluated additional markers, including CTLA-4 and GITR. Notably, we describe for the first time a chicken-specific CTLA-4 antibody, which uniquely stains CTLA-4 exclusively in intracellular (ic) compartments, distinguishing it from mammalian counterparts. Single-cell RNA sequencing further confirmed distinct FOXP3+ clusters enriched for expression of CTLA4 and TNFRSF18 (encoding GITR). While CTLA-4's ic expression limits usability in functional assays, the combination of CD4+/CD25+/CTLA-4+/GITR+ represents the most accurate characterization of putative chicken Tregs to date. These findings highlight evolutionary conservation and species-specific differences in Treg markers, providing the foundation for future studies on chicken Treg functionality.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792820","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

Decoding the Cryptic Proteome Between Antigens and Novel Functional Proteins 解码抗原和新功能蛋白之间的隐蛋白质组。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70102

Emma G. Bawden, Sebastian Amigorena, Yago A. Arribas

引用次数: 0

Hyperinflammation by Human Macrophages Induced by SARS-CoV-2 Anti-Spike IgG Is Dependent on Glucose and Fatty Acid Metabolism SARS-CoV-2抗刺突IgG诱导的人巨噬细胞高炎症依赖于葡萄糖和脂肪酸代谢

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70087

Chiara E. Geyer, Luís Almeida, Lynn Mes, Frank Otto, W. Ashwin Mak, Graham A. Heieis, Jennifer Veth, Steven W. de Taeye, Tom G. Caniels, Tom P. L. Bijl, Marit J. van Gils, Menno de Winther, Amsterdam UMC COVID-19 Biobank, Jan Van den Bossche, Hung-Jen Chen, Riekelt H. Houtkooper, Bart Everts, Jeroen den Dunnen

{"title":"Hyperinflammation by Human Macrophages Induced by SARS-CoV-2 Anti-Spike IgG Is Dependent on Glucose and Fatty Acid Metabolism","authors":"Chiara E. Geyer, Luís Almeida, Lynn Mes, Frank Otto, W. Ashwin Mak, Graham A. Heieis, Jennifer Veth, Steven W. de Taeye, Tom G. Caniels, Tom P. L. Bijl, Marit J. van Gils, Menno de Winther, Amsterdam UMC COVID-19 Biobank, Jan Van den Bossche, Hung-Jen Chen, Riekelt H. Houtkooper, Bart Everts, Jeroen den Dunnen","doi":"10.1002/eji.70087","DOIUrl":"10.1002/eji.70087","url":null,"abstract":"Severe COVID-19 is an immunological disorder characterized by excessive immune activation following infection with SARS-CoV-2, which typically occurs around the time of seroconversion. Anti-spike IgG of critically ill COVID-19 patients induces excessive inflammation by activation of Fc gamma receptors (FcγRs) on human alveolar macrophages, leading to tissue damage, pulmonary edema, and coagulopathy. While metabolic reprogramming of immune cells is critical for the induction of inflammatory responses, still little is known about the metabolic pathways that are involved in COVID-19-specific hyperinflammation. In this study, we identified that anti-spike IgG immune complexes (ICs) induce rapid metabolic reprogramming of alveolar macrophages, which is essential for the induction of inflammation. Through functional inhibition, we identified that glycolysis, fatty acid synthesis, and pentose phosphate pathway (PPP) activation are critical for anti-spike IgG-induced hyperinflammation. Remarkably, while excessive proinflammatory cytokine production by macrophages is critically dependent on simultaneous stimulation with viral stimuli and anti-spike IgG complexes, we show that the required metabolic reprogramming is specifically driven by anti-spike IgG complexes. These findings provide new insights into the metabolic pathways driving hyperinflammation by macrophages in the context of severe COVID-19. Targeting of these pathways may reveal new possibilities to counteract pathological inflammatory responses in severe COVID-19 and related diseases.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792818","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

Serous Cavity Mast Cells Depend on the ROQUIN Paralogs 浆液腔肥大细胞依赖于ROQUIN类似物。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70110

Klaus Heger, Ali Masjedi, Assa Yeroslaviz, Theodor Zeng, Seren Baygün, Angela Vicente-Luque, Chia-I. Lien, Lena Osswald, Dieter Saur, Daniel Kovacs, Marc Schmidt-Supprian

{"title":"Serous Cavity Mast Cells Depend on the ROQUIN Paralogs","authors":"Klaus Heger, Ali Masjedi, Assa Yeroslaviz, Theodor Zeng, Seren Baygün, Angela Vicente-Luque, Chia-I. Lien, Lena Osswald, Dieter Saur, Daniel Kovacs, Marc Schmidt-Supprian","doi":"10.1002/eji.70110","DOIUrl":"10.1002/eji.70110","url":null,"abstract":"Mast cells are evolutionarily ancient immune cells located at strategic entry points for pathogens and allergens. Allergen exposure activates signal transduction pathways resembling those downstream of antigen receptors in T and B lymphocytes, leading to mast cell degranulation and cytokine secretion. The paralogous RNA-binding proteins ROQUIN-1 and ROQUIN-2 prevent aberrant T cell activation and differentiation and are cleaved upon antigen receptor engagement. Here, we investigated their roles in connective tissue mast cells using conditional gene knockout in mice. We show that ROQUIN-1 and ROQUIN-2 are dispensable for skin mast cell development and maintenance, while they are essential for serosal mast cells residing in the peritoneal and pleural cavities. Concurrent ablation of both paralogs did not affect mast cell degranulation in vitro and in vivo, nor did it alter activation-induced secretion of TNF and IL-6, cytokines that are regulated by ROQUIN proteins in other cell types. Furthermore, we globally define ROQUIN-regulated mRNAs in mast cells, and validate Runx1t1 and Ebi3 as indirect and Lfng as direct ROQUIN targets. Collectively, our results highlight the essential function of ROQUIN in connective tissue mast cells in serosal cavities.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792901","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

FcµR and IgM-Mediated Complement Activation Cooperate to Enhance Humoral Immunity FcµR和igm介导的补体激活协同增强体液免疫。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70111

Zichao Wen, Lulu Dong, Jun Liu, Qing Min, Ying Wang, Ziying Hu, Xiaoqian Feng, Chaoqun Cui, Yaxuan Li, Yingying Luan, Runyun zhang, Xin Meng, Yue Tang, Hai Zhang, Meiping Yu, Chunhui Lu, Xuzhe Wu, Jingjing Zhao, Jue Wang, Anqi Wang, Birgitta Heyman, Ji-Yang Wang

{"title":"FcµR and IgM-Mediated Complement Activation Cooperate to Enhance Humoral Immunity","authors":"Zichao Wen, Lulu Dong, Jun Liu, Qing Min, Ying Wang, Ziying Hu, Xiaoqian Feng, Chaoqun Cui, Yaxuan Li, Yingying Luan, Runyun zhang, Xin Meng, Yue Tang, Hai Zhang, Meiping Yu, Chunhui Lu, Xuzhe Wu, Jingjing Zhao, Jue Wang, Anqi Wang, Birgitta Heyman, Ji-Yang Wang","doi":"10.1002/eji.70111","DOIUrl":"10.1002/eji.70111","url":null,"abstract":"<div>\u0000 \u0000 Secretory IgM plays a pivotal role in promoting robust antigen-specific IgG responses, yet the mechanisms underlying its immune-enhancing effects remain incompletely understood. IgM functions through two distinct pathways: engagement of the IgM Fc receptor (FcµR) and activation of the classical complement pathway. However, the extent of redundancy between these pathways and their roles at different stages of B cell differentiation remains unclear. To address this, we utilized FcµR-deficient mice and Cµ13 mice, which express mutant IgM incapable of activating complement. Both strains exhibited impaired T-dependent immune responses to low-dose 4-hydroxy-3-nitrophenyl-chicken γ globulin. Remarkably, FcµR−/−Cµ13 double-mutant mice showed profound defects in antigen-specific IgG production compared with either single mutant, revealing nonredundant, synergistic roles for FcµR and complement. Mechanistically, both pathways are required for early B cell activation and expansion, promoting efficient class switch recombination, germinal center (GC) formation, and plasma cell differentiation. During the GC response, IgM BCR-mediated complement activation, but not FcµR, is required for GC B-cell proliferation, survival, and affinity maturation. In contrast, FcµR primarily enhances BCR signaling in naïve B cells through downstream PI3K-AKT and MAPK pathways. These findings define two cooperative yet distinct IgM-mediated mechanisms that promote humoral immunity and regulate B cell differentiation in vivo.\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792832","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

Optimising Recovery of Hepatic Regulatory T Cells: A Practical Guide Using ARTC2 Blockade 优化肝调节性T细胞的恢复：使用ARTC2阻断的实用指南。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70095

Caitlin Abbott, Violette Mouro, Chiara Perucchini, Chiara Vespari, Matteo Iannacone

引用次数: 0

Mastering Immunity: Antibody Feedback as a Driver of Germinal Center Fate and Vaccine Responses 掌握免疫：抗体反馈作为生发中心命运和疫苗反应的驱动因素。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-19 DOI: 10.1002/eji.70108

Shuang Liu, Yang Zhang, Kai-Michael Toellner

{"title":"Mastering Immunity: Antibody Feedback as a Driver of Germinal Center Fate and Vaccine Responses","authors":"Shuang Liu, Yang Zhang, Kai-Michael Toellner","doi":"10.1002/eji.70108","DOIUrl":"10.1002/eji.70108","url":null,"abstract":"Antibody feedback in germinal center (GC) responses plays a key role in shaping the affinity, specificity, and longevity of humoral immunity. Beyond neutralizing pathogens, antibodies influence B cell selection by modulating antigen availability and masking dominant epitopes, thereby reshaping the competitive landscape for T follicular helper (Tfh) cell support. This review outlines the current understanding of how antibody feedback governs the selection stringency and clonal evolution of GC B cells, facilitates and promotes the emergence of epitope spread, and contributes to GC shutdown. We also examine how it supports the development of broadly neutralizing antibodies. Finally, we discuss how these insights are informing next-generation vaccine strategies—including immunogen design, prime-boost regimens, and adjuvant optimization—to guide affinity maturation toward specific epitopes and overcome feedback-driven constraints. Understanding antibody feedback not only reveals fundamental principles of adaptive immunity but also offers new avenues for rational vaccine design and therapeutic immune modulation.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792873","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 Antigen Presenting Capabilities of Group 3 Innate Lymphoid Cells: Insights Into Immunogenic or Tolerogenic Outcomes for T Cells 第3组先天淋巴样细胞的抗原呈递能力：对T细胞免疫原性或耐受性结果的见解。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-18 DOI: 10.1002/eji.70103

Alessia Calabrò, Sayuri Yamazaki, Guido Ferlazzo, Stefania Campana

{"title":"The Antigen Presenting Capabilities of Group 3 Innate Lymphoid Cells: Insights Into Immunogenic or Tolerogenic Outcomes for T Cells","authors":"Alessia Calabrò, Sayuri Yamazaki, Guido Ferlazzo, Stefania Campana","doi":"10.1002/eji.70103","DOIUrl":"10.1002/eji.70103","url":null,"abstract":"Group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes distributed across both lymphoid and non-lymphoid tissues, capable of mounting rapid immune responses. They are defined by expression of the transcription factor RORγt and comprise distinct subsets, including lymphoid tissue inducer-like cells expressing major histocompatibility complex class II (MHCII). These MHCII⁺ ILC3s can directly present antigens to CD4⁺ T cells, a function regulated by the transcriptional activator CIITA through a pathway similar to thymic epithelial cells. ILC3s contribute to immune homeostasis by limiting effector T cell responses and promoting regulatory T cell differentiation. However, under the influence of distinct cytokine milieus, such as IL-1β and IFN-γ, ILC3s undergo a maturation process, upregulating costimulatory molecules and enhancing their antigen-presenting capacity to activate CD4⁺ T cells. This dual functionality is highly plastic and influenced by tissue-specific environmental cues, enabling ILC3s to adapt their immunoregulatory roles according to local context. Overall, ILC3s now emerge as critical modulators of T cell activities, balancing tolerance and activation, with significant implications for host defense, autoimmunity, inflammation, and cancer.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772940","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

Ultrasensitive Test Systems Are Required to Quantify Interferon Alpha Protein in Serum Samples 需要超灵敏的测试系统来定量血清样品中的干扰素α蛋白。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-18 DOI: 10.1002/eji.70100

Liis Haljasmägi, Sandra Meisalu, Vincent Bondet, Pärt Peterson, Darragh Duffy, Kai Kisand

引用次数: 0

Mass Cytometry-Based Approach for the Investigation of Stimulator of Interferon Genes Pathway 基于细胞计数法的干扰素基因通路刺激因子研究。

IF 3.7 3区医学

European Journal of Immunology Pub Date : 2025-12-18 DOI: 10.1002/eji.70101

Anne Reversat, Paul T. Kennedy, Anni Georghiou, Joseph R. Slupsky, Lekh N. Dahal

{"title":"Mass Cytometry-Based Approach for the Investigation of Stimulator of Interferon Genes Pathway","authors":"Anne Reversat, Paul T. Kennedy, Anni Georghiou, Joseph R. Slupsky, Lekh N. Dahal","doi":"10.1002/eji.70101","DOIUrl":"10.1002/eji.70101","url":null,"abstract":"The stimulator of interferon genes (STING) pathway plays a pivotal role in innate immunity, acting as a key sensor of cytosolic DNA to initiate type-I Interferon (IFN) and pro-inflammatory cytokine production. This pathway is essential for host defence against bacterial, viral and other pathogenic threats and has emerged as a promising therapeutic target in cancer immunotherapy. However, conventional techniques such as immunoblotting and qPCR are limited in their capacity to study STING pathway activation in complex and heterogeneous biological systems, such as tumour masses or large cell populations. Here, we describe the application of mass cytometry (CyTOF) as a cutting-edge approach to characterize the STING pathway at the sub-population level. Using a high-dimensional panel of metal-labelled antibodies targeting key STING signalling components, we achieved resolution of pathway activation across diverse immune cell populations. This approach promises novel insights into cellular heterogeneity, pathway dynamics and the interplay between STING signalling and other immune pathways and underscores the power of high-dimensional analysis to overcome the limitations of traditional methods to enable a more comprehensive exploration of immune signalling pathways.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 12","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772885","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