European Journal of Immunology最新文献

{"title":"Monocyte-Platelet Aggregates Are Major Source of BDNF after Bacterial Stimulation of Human Peripheral Blood Immune Cells","authors":"Fabien Sarcletti,&nbsp;Marco Dijmarescu,&nbsp;Michael Eigenschink,&nbsp;Nadja Wukowits,&nbsp;Barbara Oehler,&nbsp;Tanja Mayer,&nbsp;Sarah Pell,&nbsp;Anastasia Tandecki,&nbsp;David Seki,&nbsp;Andreas Spittler,&nbsp;David Berry,&nbsp;Angelika Berger,&nbsp;Lukas Wisgrill","doi":"10.1002/eji.202451538","DOIUrl":"https://doi.org/10.1002/eji.202451538","url":null,"abstract":"<p>The gut microbiota and the immune system are closely connected, influencing early-life brain development. Brain-derived neurotrophic factor (BDNF), crucial for neuronal development, has been demonstrated to be produced by certain immune cells. However, the modulation of BDNF during bacterial antigen and metabolite challenge remains elusive. We investigate the effects of bacterial-derived antigens and metabolites on BDNF secretion in human PBMCs. Although BDNF levels were altered during stimulation, a specific cellular origin of BDNF within PBMCs was indeterminate. Positive magnetic separation of monocytes eliminated both the stimulant-induced BDNF secretion and reduced monocyte-platelet aggregates. Conversely, elevated platelet counts significantly increased BDNF levels, indicating that platelets, when interacting with monocytes and exposed to bacterial antigens, are likely the dominant source of BDNF in PBMC cultures. As previously described, platelets are a crucial source of circulating peripheral blood BDNF. Our findings emphasize the importance of the interplay between immune-blood cell complexes during microbial stimulation in regulating BDNF levels. This highlights the necessity of investigating such interactions to better understand the early-life gut-brain axis.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749590","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":"Expansion of Interleukin-22-Producing Type 3 Innate Lymphoid Cells in the Gut of Tristetraprolin-Deficient Mice","authors":"Bérengère de de Toeuf,&nbsp;Maxime Melchior,&nbsp;Caroline La,&nbsp;Aresio Villanueva Alcantara,&nbsp;Abdulkader Azouz,&nbsp;Vincent Martens,&nbsp;Céline La,&nbsp;Ingrid Dubois,&nbsp;Sylvie Vande Velde,&nbsp;Lara Meyer,&nbsp;Muriel Nguyen,&nbsp;Séverine Thomas,&nbsp;Frédérick Libert,&nbsp;Laure Dumoutier,&nbsp;Perry J. Blackshear,&nbsp;Stanislas Goriely","doi":"10.1002/eji.202350892","DOIUrl":"https://doi.org/10.1002/eji.202350892","url":null,"abstract":"<div>\u0000 \u0000 <p>Tristetraprolin (TTP, encoded by <i>Zfp36</i>) is an RNA-binding protein that plays a major role in the control of inflammation. <i>Zfp36^−/−</i> mice spontaneously develop a complex multiorgan inflammatory syndrome but no overt intestinal inflammation, suggesting the involvement of local regulatory mechanisms. In this study, we observed local expansion of IL-22-producing type 3 innate lymphoid cells (ILC3s) in the lamina propria of <i>Zfp36^−/−</i> mice. Our findings demonstrate that this expansion was primarily influenced by cell-extrinsic cues. In the absence of IL-22, we observed delayed onset of arthritis in <i>Zfp36^−/−</i> mice but no clear evidence of exacerbated intestinal inflammation under steady-state conditions. However, we show that <i>Zfp36^−/−</i> mice were paradoxically protected from dextran sulfate sodium (DSS)-induced colitis and suggest that increased IL-22 production by ILC3 might contribute to this observation. Taken together, these data highlight the complex interplay between systemic inflammation and gut mucosal immune homeostasis.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749686","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":"yEFIS with EFIS Lead the Way to ECR Engagement at ECI2024","authors":"Mitchell A. Pallett,&nbsp;Iva Benešová,&nbsp;Rebecca Katharina Masanetz,&nbsp;Melissa M. J. van Gool,&nbsp;Marie-Louise Diefenbach-Wilke,&nbsp;Annika Hausmann,&nbsp;Myriam Nabhan","doi":"10.1002/eji.202551844","DOIUrl":"https://doi.org/10.1002/eji.202551844","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749594","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":"Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities","authors":"Órlaith C. Henry,&nbsp;Luke A. J. O'Neill","doi":"10.1002/eji.202451381","DOIUrl":"https://doi.org/10.1002/eji.202451381","url":null,"abstract":"<p>Metabolic reprogramming of stromal cells, including fibroblast-like synoviocytes (FLS) and chondrocytes, as well as osteoclasts (OCs), are involved in the inflammatory and degenerative processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, FLS exhibit mTOR activation, enhanced glycolysis and reduced oxidative phosphorylation, fuelling inflammation, angiogenesis, and cartilage degradation. In OA, chondrocytes undergo metabolic rewiring, characterised by mTOR and NF-κB activation, mitochondrial dysfunction, and increased glycolysis, which promotes matrix metalloproteinase production, extracellular matrix (ECM) degradation, and angiogenesis. Macrophage-derived immunometabolites, including succinate and itaconate further modulate stromal cell function, acting as signalling molecules that modulate inflammatory and catabolic processes. Succinate promotes inflammation whilst itaconate is anti-inflammatory, suppressing inflammatory joint disease in models. Itaconate deficiency also correlates inversely with disease severity in RA in humans. Emerging evidence highlights the potential of targeting metabolic processes as promising therapeutic strategies for connective tissue disorders.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749591","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":"PLC and PAD2 Regulate Extracellular Calcium-Triggered Release of Macrophage Extracellular DNA Traps","authors":"Neha Mishra,&nbsp;Magdalena Mohs,&nbsp;Nico Wittmann,&nbsp;Stefan Gross,&nbsp;Paul R. Thompson,&nbsp;Lukas Bossaller","doi":"10.1002/eji.202350942","DOIUrl":"https://doi.org/10.1002/eji.202350942","url":null,"abstract":"<p>Macrophages can respond to infection or cellular stress by forming inflammasomes or by releasing extracellular traps (ETs) of DNA through METosis. While ETs have been extensively studied in neutrophils, there are fewer studies on METosis. We show that extracellular calcium and LPS enable human monocyte-derived macrophages (hMDM) to release extracellular DNA decorated with myeloperoxidase (MPO) and citrullinated histone, alongside ASC aggregation and IL-1ß maturation, indicating NLRP3 inflammasome activation. Compared with m-CSF differentiated macrophages only gm-CSF differentiated macrophages expressed macrophage elastase (MMP12) and METs released by the latter had significantly more bactericidal activity toward <i>E. coli</i>. Mechanistically, phospholipase C and peptidyl arginine deiminase-2 inhibition attenuate MET release. Interestingly, NLRP3 inflammasome blockade by MCC950 had a significant effect on MET release. Finally, MET release was completely blocked by plasma membrane stabilization by punicalagin. Altogether, we demonstrate that extracellular calcium-activated hMDM extrude DNA, containing citrullinated histones, MPO, MMP12, and ASC specks and released METs kill bacteria independent of hMDM phagocytotic activity. We believe that calcium-activated hMDM adds a physiologically relevant condition to calcium ionophore induced cell death that may be important in autoimmunity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350942","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749626","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":"Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response","authors":"Jing Wang,&nbsp;Gui-Xin Ruan,&nbsp;Yuxing Li,&nbsp;Xiong Xiao,&nbsp;Zhijian Zhu,&nbsp;Wenjing Chen,&nbsp;Hengjun Huang,&nbsp;Rui Zhang,&nbsp;Ruisi Wang,&nbsp;Meiyuan Chen,&nbsp;Ling Guo,&nbsp;Yan Li,&nbsp;Shengli Xu,&nbsp;Xijun Ou","doi":"10.1002/eji.202451508","DOIUrl":"https://doi.org/10.1002/eji.202451508","url":null,"abstract":"<div>\u0000 \u0000 <p>Germinal center (GC) response ensures the generation of diverse and high-affinity antibodies during the T cell-dependent (TD) immune response. This process is controlled by coordinated transcriptional and posttranscriptional gene regulatory mechanisms. Minor intron splicing is known to be involved in posttranscriptional regulation of gene expression. RNA-binding region (RNP1, RRM) containing 3 (RNPC3) is a minor spliceosome component involved in stabilizing the U11/U12 di-snRNP complex, which is essential for minor intron splicing. However, it remains unclear if RNPC3 and RNPC3-related gene regulatory mechanisms are important for the TD immune response. In this study, we conditionally ablated RNPC3 in activated B cells and showed that the mutant mice had defective antibody generation due to impaired GC B cell response. We demonstrate that RNPC3 deficiency inhibits the proliferation and promotes the apoptosis of activated B cells. Mechanistically, we show that RNPC3 regulates the development of GC B cells in a minor spliceosome-dependent manner by controlling the removal of minor introns from minor intron-containing genes associated with cell proliferation and apoptosis. Our study thus uncovers a previously unappreciated role for RNPC3 in regulating GC B cell response.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749593","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":"Guidelines and Advances in Basic and Applied Dendritic Cell Biology","authors":"Björn E. Clausen,&nbsp;Diana Dudziak","doi":"10.1002/eji.202551942","DOIUrl":"https://doi.org/10.1002/eji.202551942","url":null,"abstract":"&lt;p&gt;Dear Readers,&lt;/p&gt;&lt;p&gt;The Study Group Dendritic Cells (AKDC) of the German Society for Immunology (DGfI), established on September 28, 2016, during the 46th Annual Meeting in Hamburg, has become an essential forum for fostering high-quality research in dendritic cell (DC) and macrophage biology. With a current membership of 342, the group emphasizes rigorous scientific inquiry, methodological standardization, and active collaboration between young and established investigators.&lt;/p&gt;&lt;p&gt;The research interests of the AKDC cover a wide spectrum of topics within DC and macrophage biology, addressing fundamental issues from ontogeny and tissue homeostasis to T cell priming and immune regulation. Importantly, the research initiatives extend into translational applications, aiming to harness these cells in therapeutic strategies against cancer and autoimmune diseases. This integrated approach underscores the dual commitment to understanding the cellular mechanisms underpinning immune responses and translating these insights into clinical innovation.&lt;/p&gt;&lt;p&gt;A notable initiative that emerged from the activities of the AKDC is this special collection of articles on DCs. This collection compiles recent key developments and technical advances in the field, providing a critical resource for researchers to keep pace with emerging methodologies and conceptual frameworks. The series not only highlights advances in basic DC biology but also lays the groundwork for applied research, thereby serving as a bridge between laboratory discoveries and clinical application.&lt;/p&gt;&lt;p&gt;Central to the AKDC's contributions are the hands-on laboratory protocols (&lt;i&gt;Guidelines&lt;/i&gt;) that standardize the preparation and analysis of DC subsets. One set of guidelines details the preparation of single-cell suspensions from mouse lymphoid tissues—including the spleen, lymph nodes, and thymus—and describes the subsequent multiparameter flow cytometry analysis designed to differentiate DC subsets from other myeloid cells. Complementary protocols address the preparation of single-cell suspensions from mouse nonlymphoid tissues, such as skin, intestine, lung, kidney, mammary glands, oral mucosa, and transplantable tumors, ensuring that a wide range of experimental systems can benefit from reproducible methodologies.&lt;/p&gt;&lt;p&gt;The guidelines further extend into human studies, where protocols for the preparation of single-cell suspensions from human lymphoid and nonlymphoid tissues are detailed. These protocols include detailed gating strategies for flow cytometric analysis and cell sorting, thereby enhancing the resolution at which primary human DC subpopulations can be examined. In addition, state-of-the-art protocols for multiparameter fluorescence microscopy have been developed to facilitate the visualization and quantitative analysis of DC subsets within tissue sections, further advancing our capacity to analyze these cells in situ.&lt;/p&gt;&lt;p&gt;Beyond these technical protocols, the article collection","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551942","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749372","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":"IgA2 ACPA Drives a Hyper-Inflammatory Phenotype in Macrophages via ATP Synthase and COX2","authors":"Luís Almeida,&nbsp;Alice Bacon,&nbsp;Mohan Ghorasaini,&nbsp;Alwin J. van der Ham,&nbsp;René E. M. Toes,&nbsp;Martin Giera,&nbsp;Bart Everts","doi":"10.1002/eji.202451586","DOIUrl":"https://doi.org/10.1002/eji.202451586","url":null,"abstract":"<p>IgA can form immune complexes (ICs) and activate myeloid cells via Fc alpha receptor-mediated signalling to secrete pro-inflammatory cytokines. It was previously described that of the two IgA subclasses (IgA1 and IgA2), IgA2 is more inflammatory than IgA1. However, the mechanisms underlying this differential pro-inflammatory potential remain poorly defined. Using anti-citrullinated protein IgA1 and IgA2 antibodies (ACPA) that are commonly found in rheumatoid arthritis (RA) patients and linked to chronic inflammation, we show here that, in macrophages, IgA2-ICs boost TLR-induced TNF and IL6 secretion, COX2 expression, and production of COX2-dependent lipid mediators to a higher level than IgA1-ICs. Metabolically, we found the amplification of TLR-induced cytokine production and COX2 induction by IgA2-ICs to be dependent on mitochondrial ATP synthesis, but not glycolysis. Finally, we found the potentiation of TLR-induced cytokine production by IgA-ICs to be COX2-dependent. Together this work points towards a key role for mitochondrial ATP synthesis in driving COX2 expression and subsequent IgA2-IC-dependent potentiation of TLR-induced cytokine production by macrophages. As such, our work provides new insights into the mechanisms underlying IgA2-induced inflammation in the context of RA. Thus, this may hold novel clues to be explored as therapeutic possibilities to target antibody-driven inflammation in chronic inflammatory diseases.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749595","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. 4'25","authors":"","doi":"10.1002/eji.202570041","DOIUrl":"https://doi.org/10.1002/eji.202570041","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":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741059","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":"Modulation of Host Immunity by Microbiome-Derived Indole-3-Propionic Acid and Other Bacterial Metabolites","authors":"Burkhard Schütz,&nbsp;Felix F. Krause,&nbsp;R. Verena Taudte,&nbsp;Mario M. Zaiss,&nbsp;Maik Luu,&nbsp;Alexander Visekruna","doi":"10.1002/eji.202451594","DOIUrl":"https://doi.org/10.1002/eji.202451594","url":null,"abstract":"<p>In recent years, we have witnessed a rapidly growing interest in the intricate communications between intestinal microorganisms and the host immune system. Research on the human microbiome is evolving from merely descriptive and correlative studies to a deeper mechanistic understanding of the bidirectional interactions between gut microbiota and the mucosal immune system. Despite numerous challenges, it has become increasingly evident that an imbalance in gut microbiota composition, known as dysbiosis, is associated with the development and progression of various metabolic, immune, cancer, and neurodegenerative disorders. A growing body of evidence highlights the importance of small molecules produced by intestinal commensal bacteria, collectively referred to as gut microbial metabolites. These metabolites serve as crucial diffusible messengers, translating the microbial language to host cells. This review aims to explore the complex and not yet fully understood molecular mechanisms through which microbiota-derived metabolites influence the activity of the immune cells and shape immune reactions in the gut and other organs. Specifically, we will discuss recent research that reveals the close relationship between microbial indole-3-propionic acid (IPA) and mucosal immunity. Furthermore, we will emphasize the beneficial effects of IPA on intestinal inflammation and discuss its potential clinical implications.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749625","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}