Tamar Ratishvili, Iana H. Haralambieva, Huy Q. Quach, Ilya M. Swanson, Krista M. Goergen, Diane E. Grill, Inna G. Ovsyannikova, Richard B. Kennedy, Gregory A. Poland
{"title":"Transcriptomic Signatures Predict Rubella Virus-Induced Cytokine and Chemokine Responses in Female MMR Recipients","authors":"Tamar Ratishvili, Iana H. Haralambieva, Huy Q. Quach, Ilya M. Swanson, Krista M. Goergen, Diane E. Grill, Inna G. Ovsyannikova, Richard B. Kennedy, Gregory A. Poland","doi":"10.1002/eji.202451303","DOIUrl":"https://doi.org/10.1002/eji.202451303","url":null,"abstract":"<p>The study examined the relationship between rubella virus (RV)-induced gene expression and proinflammatory cytokine/chemokine secretion in females previously vaccinated with MMR. Gene clusters enriched for functional pathways of innate immune system activation and antiviral responses were found to predict RV-specific MCP-1, MCP-4, IP-10, and IL-2 secretion.\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 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380556","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":"Cover Story: Eur. J. Immunol. 2'25","authors":"","doi":"10.1002/eji.202570021","DOIUrl":"https://doi.org/10.1002/eji.202570021","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 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380013","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":"Striking the Right Chord at EJI: Introducing Editor-in-Chief Matteo Iannacone and the Seamless Transfer Policy","authors":"Matteo Iannacone, Nadja Bakocevic","doi":"10.1002/eji.202551784","DOIUrl":"10.1002/eji.202551784","url":null,"abstract":"<p>Matteo Iannacone received his M.D. from the University of Milan, completed a residency in Internal Medicine, and earned a Ph.D. in Immunology at Vita-Salute San Raffaele University in Milan, Italy. After postdoctoral training at The Scripps Research Institute (La Jolla, CA) and at Harvard Medical School (Boston, MA), he returned to Milan, where he now serves as Director of the Division of Immunology, Transplantation, and Infectious Diseases, Professor of pathology, and Head of the Dynamics of Immune Responses Laboratory at the San Raffaele Scientific Institute and University. Having joined EJI's Executive Committee in 2021, he takes on the role of EJI's academic Editor-in-Chief starting January 2025.</p><p>My laboratory's work centers on understanding how immune responses are orchestrated within local tissue niches. Recent breakthroughs in intravital imaging and spatially resolved omics have enabled us to visualize and quantify interactions at cellular resolution in living organisms, revealing unprecedented details about how immune cells—and even nonimmune cells—behave and communicate.</p><p>In our lab, we combine these powerful tools—high-resolution imaging, single-cell sequencing, and advanced computational analyses—to dissect how local processes converge to influence immune outcomes. By focusing on phenomena such as how T cells exert immune surveillance and examining immunological crosstalk across different tissues, we aim to bridge the gap between discrete molecular events and broader physiological consequences. This holistic perspective is particularly relevant in complex conditions like infectious diseases and cancer, where local cell-to-cell interactions can be a pivotal driver of disease progression. Ultimately, our goal is to uncover novel principles of tissue immunity and leverage them for more precise immunotherapeutic strategies.</p><p>I have a long-standing appreciation for the <i>European Journal of Immunology</i> (EJI). Early in my career, I would often turn to EJI as a reliable source of rigorous immunological research. The journal's commitment to quality and its role in the global immunology community resonate strongly with my own vision. Furthermore, my time on the Executive Committee allowed me to be actively involved in strategic decisions. I feel privileged to succeed outstanding leaders, including our outgoing Editor-in-Chief, Chiara Romagnani, and to continue the legacy of excellence set by Jim Di Santo, whose 9-year term was remarkable. I am grateful to the entire EJI team for preserving the journal's values and scientific rigor through all kinds of challenges.</p><p>At the heart of my editorial vision lies a firm commitment to publishing rigorous, high-quality science while fostering an author-friendly environment. We have recently updated policies to enhance transparent communication between referees and authors, and we continue to strengthen our ties with EFIS to support young immunologists. Building on past success,","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062178","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":"The Anti-Human P2X7 Monoclonal Antibody (Clone L4) Can Mediate Complement-Dependent Cytotoxicity of Human Leukocytes","authors":"Amal Elhage, Debbie Watson, Ronald Sluyter","doi":"10.1002/eji.202451196","DOIUrl":"10.1002/eji.202451196","url":null,"abstract":"<p>P2X7 is an extracellular adenosine 5′-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2<sub>b</sub> antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown. In this study the functionality of this mAb was confirmed by inhibition of ATP-induced Ca<sup>2+</sup> responses in HEK-293 cells expressing P2X7 (HEK-P2X7). Spectrophotometric measurements of lactate dehydrogenase release demonstrated that the anti-P2X7 mAb mediated CDC in HEK-P2X7 but not HEK-293 cells. Further, flow cytometric measurements of the viability dye, 7-aminoactinomycin D, showed that this mAb mediated CDC in human RPMI 8226 but not mouse J774 cells. Immunolabelling with this mAb and flow cytometry revealed that relative amounts of cell surface P2X7 varied between human peripheral blood leukocytes. As such, the anti-P2X7 mAb preferentially mediated CDC of leukocytes that displayed relatively high cell surface P2X7, namely monocytes, DCs, natural killer T cells, myeloid-derived suppressor cells, and T helper 17 cells. Together, this data highlights a novel approach to target cellular P2X7 and to limit unwanted P2X7 functions.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031681","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}
Michelle Broekhuizen, Marie-Louise van der Hoorn, Disha Vadgama, Michael Eikmans, Bojou J. Neecke, Johannes J. Duvekot, Pieter Fraaij, Irwin K. M. Reiss, Dana A. M. Mustafa, Lotte E. van der Meeren, Sam Schoenmakers
{"title":"Similar Spatial Expression of Immune-Related Proteins in SARS-CoV-2 Placentitis and Chronic Histiocytic Intervillositis","authors":"Michelle Broekhuizen, Marie-Louise van der Hoorn, Disha Vadgama, Michael Eikmans, Bojou J. Neecke, Johannes J. Duvekot, Pieter Fraaij, Irwin K. M. Reiss, Dana A. M. Mustafa, Lotte E. van der Meeren, Sam Schoenmakers","doi":"10.1002/eji.202451386","DOIUrl":"10.1002/eji.202451386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the placenta can lead to fetal distress and demise, characterized by severe trophoblast necrosis, chronic histiocytic intervillositis (CHI), and massive perivillous fibrin deposition. We aimed to uncover spatial immune-related protein changes in SARS-CoV-2 placentitis compared with CHI placentas and uncomplicated pregnancies to gain insight into the underlying pathophysiological mechanisms. Placentas were retrospectively collected from cases with SARS-CoV-2 placentitis resulting in fetal distress/demise (<i>n</i> = 9), CHI (<i>n</i> = 9), and uncomplicated term controls (<i>n</i> = 9). The expression of 53 immune-related proteins was quantified using GeoMx Digital Spatial Profiler in three separate compartments: villi (fetal compartment), intervillous space, and decidua (both maternal compartments). Compared with controls, SARS-CoV-2 placentitis and CHI both displayed differentially expressed proteins in the intervillous space only, including upregulation of myeloid markers (e.g., CD40, CD11c, CD68, CD163). Specifically, SARS-CoV-2 placentitis was associated with reduced expression of multiple apoptotic proteins (e.g., BAD, BIM, BLXL, BCL6). In conclusion, SARS-CoV-2 placentitis and CHI are associated with enhanced myeloid cell infiltration into the intervillous space, but not in the decidua and villi. The more prominently reduced apoptosis-related protein expression in SARS-CoV-2 placentitis may lead to an exaggerated immune response, causing acute placental dysfunction and fetal demise.</p>\u0000 </section>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996980","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}
Sanne Kroos, Nienke J. Blomberg, Joanneke C. Kwekkeboom, Rudi W. Hendriks, Odilia B. J. Corneth, René E. M. Toes, Hans U. Scherer
{"title":"Increased Phosphorylation of Intracellular Signaling Molecules Indicates Continuous Activation of Human Autoreactive B-Cells","authors":"Sanne Kroos, Nienke J. Blomberg, Joanneke C. Kwekkeboom, Rudi W. Hendriks, Odilia B. J. Corneth, René E. M. Toes, Hans U. Scherer","doi":"10.1002/eji.202451361","DOIUrl":"10.1002/eji.202451361","url":null,"abstract":"<p>Many human autoimmune diseases (AIDs) are hallmarked by the presence and persistence of autoreactive B-cells. While autoreactive B-cells may frequently encounter antigens, the signals required to balance and maintain their activation and survival are mostly unknown. Understanding such signals may be important for strategies aimed at eliminating human B-cell autoreactivity. Here, we assessed intracellular signaling pathways in B cells targeting citrullinated protein antigens isolated from patients with rheumatoid arthritis (RA), a common and well-characterized AID. Peripheral blood mononuclear cells of 15 RA patients positive for anti-citrullinated protein antibodies (ACPA) were analyzed directly ex vivo using spectral flow cytometry and B-cell differentiation markers, citrullinated antigen-biotin-streptavidin tetramers, and intracellular (phosphoflow) markers. Tetanus toxoid (TT)-specific B cells served as antigen-specific comparators. In absence of any in vitro BCR stimulation, ACPA-expressing memory B cells (MBCs) displayed enhanced expression of Ki-67 and increased SYK-, BTK-, AKT-, and S6-phosphorylation compared with TT-specific MBCs. We demonstrate the simultaneous detection of B cell antigen-specificity and intracellular protein phosphorylation on the single-cell level. The data reveal that autoreactive B-cells in RA, in contrast to B cells against recall antigens, display enhanced phosphorylation of signaling molecules that point toward continuous, presumably antigen-mediated activation of the autoreactive B-cell compartment.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996975","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":"TSLP and TSLPr Expression and Localization in the Airways of COPD and Non-COPD Patients","authors":"Lynda Saber Cherif, Maëva A Devilliers, Jeanne-Marie Perotin, Julien Ancel, Alexandre Vivien, Arnaud Bonnomet, Gonzague Delepine, Anne Durlach, Myriam Polette, Gaëtan Deslée, Valérian Dormoy","doi":"10.1002/eji.202451480","DOIUrl":"10.1002/eji.202451480","url":null,"abstract":"<div>\u0000 \u0000 <p>Thymic stromal lymphopoietin (TSLP) is an alarmin cytokine activated by allergens, pathogens, and air pollutants. Recent studies suggest TSLP dysregulation in chronic inflammatory diseases. It was highlighted as a key player in the context of asthma-associated mucosal immunity. This study investigated the production and localization of TSLP and its receptors in airway epithelial cells and the related inflammatory response in chronic obstructive pulmonary disease (COPD) and non-COPD patients. TSLP transcripts and proteins were detected in epithelial cells but were not abundant at a steady state. The secretion of airway inflammatory mediators was altered in COPD in association with TSLP production. The cellular and molecular characterization of TSLP signaling may identify COPD patients that could benefit from anti-alarmin therapeutic approaches.\u0000</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996983","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}
Zehra Uyar-Aydin, Shirin Kadler, Roland Lauster, Sina Bartfeld, Mark Rosowski
{"title":"Survival of Human Bone Marrow Plasma Cells In Vitro Depends on the Support of the Stromal Cells, PI3K, and Canonical NF-kappaB Signaling","authors":"Zehra Uyar-Aydin, Shirin Kadler, Roland Lauster, Sina Bartfeld, Mark Rosowski","doi":"10.1002/eji.202451358","DOIUrl":"10.1002/eji.202451358","url":null,"abstract":"<p>Contrary to short-lived plasma cells, which survive only 3–5 days, long-lived plasma cells (LLPCs) contribute to the humoral memory of the body and thus also to many antibody-related diseases. The ability of plasma cells to persist over months, years, and even a lifetime has been demonstrated in vivo. Yet, the in vitro culture of human primary bone marrow-derived plasma cells has been limited to a few days. Here, we establish culture conditions for human primary bone marrow-derived plasma cells for 21 days. Plasma cells and stromal cells are isolated from human bone marrow and cultured in 2D or a 3D ceramic scaffold. The plasma cells’ survival and antibody secretion depend on direct contact with stromal cells. The culture promotes CD19-negative PCs. Inhibition of the PI3K or NF-kappaB pathways using chemical inhibitors reduced the survival of the plasma cells. These results underline the supportive role of the stromal cells for the survival of the LLPC and confirm mechanisms that were identified in mouse LLPCs also for human LLPCs. The culture described here will promote further studies to deepen our understanding of the human LLPC.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941729","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. 1'25","authors":"","doi":"10.1002/eji.202570011","DOIUrl":"https://doi.org/10.1002/eji.202570011","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 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113136","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}